Engineered muscle targeting compositions
Engineered AAV vectors with muscle-targeting moieties address the limitations of conventional rAAVs by enhancing cell specificity and transduction efficiency, reducing dosage needs and liver toxicity, and improving species consistency.
Patent Information
- Authority / Receiving Office
- US · United States
- Patent Type
- Applications(United States)
- Current Assignee / Owner
- THE BROAD INST INC
- Filing Date
- 2025-11-14
- Publication Date
- 2026-05-07
AI Technical Summary
Conventional recombinant adeno-associated viruses (rAAVs) exhibit limited cell tropism, requiring high doses for effective delivery to non-liver tissues like nervous and cardiac muscle, leading to liver toxicity and manufacturing challenges, and species-specific transduction efficiency varies, making preclinical mouse studies less predictive for human outcomes.
Engineered AAV vectors with muscle-targeting moieties, such as RGD motifs, are developed to enhance cell specificity and reduce dosage requirements, utilizing n-mer motifs inserted into viral capsids to improve transduction efficiency and reduce immunogenicity.
The engineered AAV vectors demonstrate increased muscle cell potency and specificity, reducing the need for high doses, minimizing liver toxicity, and providing consistent results across species, including humans.
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Figure US20260125706A1-D00000_ABST
Abstract
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent application Ser. No. 17 / 764,509, filed on Mar. 28, 2022, which is the U.S. National Stage Application under 35 U.S.C. § 371 of Patent Cooperation Treaty Application No.: PCT / US2020 / 056133, filed on Oct. 16, 2020. Patent Cooperation Treaty Application No.: PCT / US2020 / 056133 claims the benefit of and priority to U.S. Provisional Patent Application Nos. 62 / 916,207, filed on Oct. 16, 2019; entitled “Engineered Adeno-Associated Virus Capsids”; 62 / 916,221, filed on Oct. 16, 2019, entitled “Engineered Adeno-Associated Virus Capsids”; 63 / 018,454, filed on Apr. 30, 2020, entitled “Engineered Adeno-Associated Virus Capsids”; and 63 / 055,252, filed on Jul. 22, 2020, entitled “Engineered Muscle Targeting Compositions”. The contents of the above-identified applications are hereby fully incorporated herein by reference in their entireties.SEQUENCE LISTING
[0002] The contents of the electronic sequence listing (“BROD-5005US-CON3_ST26.xml”; size is 11,165,381 bytes and it was created on Nov. 14, 2025) is herein incorporated by reference in its entirety.TECHNICAL FIELD
[0003] The subject matter disclosed herein is generally directed to muscle targeting compositions including, but not limited to, recombinant adeno-associated virus (AAV) vectors and systems thereof, compositions, and uses thereof.BACKGROUND
[0004] Recombinant AAVs (rAAVs) are the most commonly used delivery vehicles for gene therapy and gene editing. Nonetheless, rAAVs that contain natural capsid variants have limited cell tropism. Indeed, rAAVs used today mainly infect the liver after systemic delivery. Further, the transduction efficiency of conventional rAAVs in other cell-types, tissues, and organs by these conventional rAAVs with natural capsid variants is limited. Therefore, AAV-mediated polynucleotide delivery for diseased that affect cells, tissues, and organs other than the liver (e.g. nervous system, skeletal muscle, and cardiac muscle) typically requires an injection of a large dose of virus (typically about 1×1014 vg / kg), which often results in liver toxicity. Furthermore, because large doses are required when using conventional rAAVs, manufacturing sufficient amounts of a therapeutic rAAV needed to dose adult patients is extremely challenging. Additionally, due to differences in gene expression and physiology, mouse and primate models respond differently to viral capsids. Transduction efficiency of different virus particles varies between different species, and as a result, preclinical studies in mice often do not accurately reflect results in primates, including humans. As such, there exists a need for improved rAAVs for use in the treatment of various genetic diseases.SUMMARY
[0005] Described in certain example embodiments herein are compositions comprising a targeting moiety effective to target a muscle cell, wherein the targeting moiety comprises an n-mer motif, and a cargo, wherein the cargo is coupled to or is otherwise associated with the targeting moiety.
[0006] In certain example embodiments, the n-mer motif comprises an RGD motif or a non-RGD n-mer motif.
[0007] In certain example embodiments, the RGD motif has a formula of XmRGDXn, wherein m is 0-4 amino acids, wherein n is 0-15 amino acids, wherein X is any amino acid, and wherein each X amino acid present is independently selected from the others from the group consisting of: any amino acid.
[0008] In certain example embodiments, the RGD motif has the formula RGDXn, wherein n is 4 or 5, wherein X is any amino acid, and wherein each X amino acid present is independently selected from the others from the group consisting of: any amino acid.
[0009] In certain example embodiments, the n-mer motif is any one of SEQ ID NO: 13-50, 1277-2493, 3737-4979, 6647-8313, 8314-8502, or 8692-8889.
[0010] In certain example embodiments, the targeting moiety comprises a polypeptide, a polynucleotide, a lipid, a polymer, a sugar, or a combination thereof.
[0011] In certain example embodiments, the targeting moiety comprises a viral protein.
[0012] In certain example embodiments, the viral protein is a capsid protein.
[0013] In certain example embodiments, the viral protein is an adeno associated virus (AAV) protein.
[0014] In certain example embodiments, the n-mer motif is located between two amino acids of the viral protein such that the n-mer motif is external to a viral capsid of which the viral capsid protein is part.
[0015] In certain example embodiments, the n-mer motif is inserted between any two contiguous amino acids between amino acids 262-269, 327-332, 382-386, 452-460, 488-505, 527-539, 545-558, 581-593, 704-714, or any combination thereof in an AAV9 capsid polypeptide or in an analogous position in an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV rh.74, or AAV rh.10 capsid polypeptide.
[0016] In certain example embodiments, the n-mer motif is inserted between amino acids 588 and 589 in an AAV9 capsid polypeptide or in an analogous position in an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV rh.74, or AAV rh.10 capsid polypeptide.
[0017] In certain example embodiments, the composition is an engineered viral particle.
[0018] In certain example embodiments, the engineered viral particle is an engineered AAV viral particle.
[0019] In certain example embodiments, the AAV viral particle is an engineered AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV rh.74, or AAV rh.10 viral particle.
[0020] In certain example embodiments, the cargo is capable of treating or preventing a muscle disease or disorder.
[0021] In certain example embodiments, the muscle disease or disorder is
[0022] a. an auto immune disease;
[0023] b. a cancer;
[0024] c. a muscular dystrophy;
[0025] d. a neuro-muscular disease;
[0026] e. a sugar or glycogen storage disease;
[0027] f. an expanded repeat disease;
[0028] g. a dominant negative disease;
[0029] h. a cardiomyopathy;
[0030] i. a viral disease;
[0031] j. a progeroid disease; or
[0032] k. any combination thereof.
[0033] In certain example embodiments, the cargo is
[0034] a. a morpholino;
[0035] b. a peptide-linked morpholino;
[0036] c. an antisense oligonucleotide;
[0037] d. a PMO, a therapeutic transgene;
[0038] e. a polynucleotide encoding a therapeutic polypeptide or peptide;
[0039] f. a PPMO;
[0040] g. one or more peptides or polypeptides;
[0041] h. one or more polynucleotides encoding a CRISPR-Cas protein, a guide RNA, or both;
[0042] i. a ribonucleoprotein, wherein the ribonucleoprotein comprises a CRISPR-Cas system molecule;
[0043] j. a therapeutic transgene RNA, or other gene modifying or therapeutic RNA and / or protein; or
[0044] k. any combination thereof.
[0045] In certain example embodiments, the cargo is capable of inducing exon skipping in a gene.
[0046] In certain example embodiments, the cargo is capable of inducing exon skipping in a dystrophin gene.
[0047] In certain example embodiments, the cargo is a mini- or micro-dystrophin gene.
[0048] In certain example embodiments, the mini- or micro-dystrophin gene comprises spectrin-like repeats 1, 1′, 2, 3, 16, 17, 20, 21, 22, 23, 24, or any combination thereof, and optionally an nNOS domain, an actin binding domain, one or more hinge regions, a dystroglycan binding domain, or any combination thereof.
[0049] In certain example embodiments, the cargo is operably coupled to a muscle specific promoter.
[0050] In certain example embodiments, the expanded repeat disease is Huntington's disease, a Myotonic Dystrophy, or Facioscapulohumeral muscular dystrophy (FSHD).
[0051] In certain example embodiments, the muscular dystrophy is Duchene muscular dystrophy, Becker Muscular dystrophy, a Limb-Girdle muscular dystrophy, an Emery Dreifuss muscular dystrophy, a myotonic dystrophy, or FSHD.
[0052] In certain example embodiments, the myotonic dystrophy is a Type 1 or a Type 2 myotonic dystrophy.
[0053] In certain example embodiments, the cardiomyopathy is dilated cardiomyopathy, hypertrophic cardiomyopathy, Duchene muscular dystrophy-associated cardiomyopathy, or Dannon disease.
[0054] In certain example embodiments, the sugar or glycogen storage disease is a MPS type III disease or Pompe disease.
[0055] In certain example embodiments, the MPS type III disease, is MPS Type IIIA, IIIB, IIIC, or IIID.
[0056] In certain example embodiments, the neuro-muscular disease is Charcot-Marie-Tooth disease or Friedreich's Ataxia.
[0057] In certain example embodiments, the composition has increased muscle cell potency, muscle cell specificity, reduced immunogenicity, or any combination thereof.
[0058] Described in certain example embodiments herein are vector systems comprising a vector comprising: one or more polynucleotides each encoding all or part of one or more targeting moieties effective to target a muscle cell, wherein each targeting moiety comprises one or more n-mer motifs, wherein each n-mer motif an RGD motif or a non-RGD n-mer motif, and wherein each polynucleotide at least encodes one or more of the one or more n-mer motifs; and optionally, a regulatory element operatively coupled to one or more of the one or more polynucleotides.
[0059] In certain example embodiments, the RGD motif has a formula of XmRGDXn, wherein m is 0-4 amino acids, wherein n is 0-15 amino acids, wherein X is any amino acid, and wherein each X amino acid present is independently selected from the others from the group consisting of: any amino acid.
[0060] In certain example embodiments, the RGD motif has the formula RGDXn, wherein n is 4 or 5, wherein X is any amino acid, and wherein each X amino acid present is independently selected from the others from the group consisting of: any amino acid.
[0061] In certain example embodiments, the n-mer motif is any one of SEQ ID NO: 13-50, 1277-2493, 3737-4979, 6647-8313, 8314-8502, or 8692-8889.
[0062] In certain example embodiments, the vector system further comprises a cargo.
[0063] In certain example embodiments, the cargo is a cargo polynucleotide and is optionally coupled to one or more of the one or more polynucleotides encoding the targeting moiety, the regulatory element, or both.
[0064] In certain example embodiments, the cargo polynucleotide is present on the same vector or a different vector as the one or more polynucleotides encoding the targeting moiety.
[0065] In certain example embodiments, the vector system is capable of producing virus particles that contain the cargo.
[0066] In certain example embodiments, the vector system is capable of producing a viral capsid polypeptide comprising one or more of the targeting moieties.
[0067] In certain example embodiments, the vector system is capable of producing AAV virus particles.
[0068] In certain example embodiments, AAV viral particles are engineered AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV rh.74, or AAV rh.10 viral particle.
[0069] In certain example embodiments, the capsid polypeptide is an engineered AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV rh.74, AAV rh.10 capsid polypeptide.
[0070] In certain example embodiments, wherein at least one of the one or more polynucleotides encoding the n-mer motif(s) is inserted between two codons corresponding to two amino acids of the viral protein such that at least one of the n-mer motifs is external to the viral capsid.
[0071] In certain example embodiments, the two codons correspond to any two contiguous amino acids between amino acids 262-269, 327-332, 382-386, 452-460, 488-505, 527-539, 545-558, 581-593, 704-714, or any combination thereof in an AAV9 capsid polypeptide or in an analogous position in an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV rh.74, or AAV rh.10 capsid polypeptide.
[0072] In certain example embodiments, the two codons correspond to amino acid 588 and 589 in the AAV9 capsid polynucleotide or in an analogous position in an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV rh.74, or AAV rh.10 capsid polypeptide.
[0073] In certain example embodiments, the vector comprising the one or more polynucleotides each encoding all or part of one or more targeting moieties does not comprise splice regulatory elements.
[0074] In certain example embodiments, the vector system further comprises a polynucleotide encoding a viral rep protein.
[0075] In certain example embodiments, the viral rep protein is an AAV rep protein.
[0076] In certain example embodiments, the polynucleotide encoding the viral rep protein is on the same vector or different vector as the one or more polynucleotides each encoding all or part of one or more targeting moieties.
[0077] In certain example embodiments, the viral rep protein is operatively coupled to a regulatory element.
[0078] Described in certain example embodiments herein are polypeptides produced by expressing a vector system as described herein.
[0079] In certain example embodiments, the polypeptide is a viral polypeptide.
[0080] In certain example embodiments, the viral polypeptide is an AAV polypeptide.
[0081] Described in certain example embodiments herein are particles produced by expressing a vector system as described herein.
[0082] In certain example embodiments, the particle is a viral particle.
[0083] In certain example embodiments, the viral particle is an adeno-associated virus (AAV) particle.
[0084] In certain example embodiments, the viral particle has a muscle-specific tropism.
[0085] Described in certain example embodiments, a vector system as described herein, a polypeptide as described herein, or a particle as described herein, wherein the cargo is capable of treating or preventing a muscle disease or disorder.
[0086] In certain example embodiments, the muscle disease or disorder is
[0087] a. an auto immune disease;
[0088] b. a cancer;
[0089] c. a muscular dystrophy;
[0090] d. a neuro-muscular disease;
[0091] e. a sugar or glycogen storage disease;
[0092] f. an expanded repeat disease;
[0093] g. a dominant negative disease;
[0094] h. a cardiomyopathy;
[0095] i. a viral disease;
[0096] j. a progeroid disease; or
[0097] k. any combination thereof.
[0098] In certain example embodiments, the cargo is
[0099] a. a morpholino;
[0100] b. a peptide-linked morpholino;
[0101] c. an antisense oligonucleotide;
[0102] d. a PMO, a therapeutic transgene;
[0103] e. a polynucleotide encoding a therapeutic polypeptide or peptide;
[0104] f. a PPMO;
[0105] g. one or more peptides or polypeptides;
[0106] h. one or more polynucleotides encoding a CRISPR-Cas protein, a guide RNA, or both;
[0107] i. a ribonucleoprotein, wherein the ribonucleoprotein comprises a CRISPR-Cas system molecule;
[0108] j. a therapeutic transgene RNA, or other gene modifying or therapeutic RNA and / or protein; or
[0109] k. any combination thereof.
[0110] In certain example embodiments, the cargo is capable of inducing exon skipping in a gene.
[0111] In certain example embodiments, the cargo is capable of inducing exon skipping in a dystrophin gene.
[0112] In certain example embodiments, the cargo is a mini- or micro-dystrophin gene.
[0113] In certain example embodiments, the mini- or micro-dystrophin gene comprises spectrin-like repeats 1, 1′, 2, 3, 16, 17, 20, 21, 22, 23, 24, or any combination thereof, and optionally an nNOS domain, an actin binding domain, one or more hinge regions, a dystroglycan binding domain, or any combination thereof.
[0114] In certain example embodiments, the expanded repeat disease is Huntington's disease, a Myotonic Dystrophy, or Facioscapulohumeral muscular dystrophy (FSHD).
[0115] In certain example embodiments, the muscular dystrophy is Duchene muscular dystrophy, Becker Muscular dystrophy, a Limb-Girdle muscular dystrophy, an Emery Dreifuss muscular dystrophy, a myotonic dystrophy, or FSHD.
[0116] In certain example embodiments, the myotonic dystrophy is Type 1 or Type 2.
[0117] In certain example embodiments, the cardiomyopathy is dilated cardiomyopathy, hypertrophic cardiomyopathy, DMD-associated cardiomyopathy, or Dannon disease.
[0118] In certain example embodiments, the sugar or glycogen storage disease is a MPS type III disease or Pompe disease.
[0119] In certain example embodiments, the MPS type III disease, is MPS Type IIIA, IIIB, IIIC, or IIID.
[0120] In certain example embodiments, the neuro-muscular disease is Charcot-Marie-Tooth disease or Friedreich's Ataxia.
[0121] In certain example embodiments, the polypeptide, the particle, or both have increased muscle cell potency, muscle cell specificity, reduced immunogenicity, or any combination thereof.
[0122] A cell comprising:
[0123] a. a composition as described herein;
[0124] b. a vector system as described herein;
[0125] c. a polypeptide as described herein;
[0126] d. a particle as described herein; or
[0127] e. a combination thereof.
[0128] In certain example embodiments, wherein the cell is prokaryotic.
[0129] In certain example embodiments, wherein the cell is eukaryotic.
[0130] A pharmaceutical formulation comprising:
[0131] a. a composition as described herein;
[0132] b. a vector system as described herein;
[0133] c. a polypeptide as described herein;
[0134] d. a particle as described herein;
[0135] e. a cell as described herein; or
[0136] f. a combination thereof; and
[0137] a pharmaceutically acceptable carrier.
[0138] A method comprising:
[0139] administering, to a subject in need thereof, a
[0140] a. a composition as described herein;
[0141] b. a vector system as described herein;
[0142] c. a polypeptide as described herein;
[0143] d. a particle as described herein;
[0144] e. a cell as described herein;
[0145] f. a pharmaceutical formulation as described herein; or
[0146] g. a combination thereof.
[0147] In certain example embodiments, the subject in need thereof has a muscle disease or disorder.
[0148] In certain example embodiments, the muscle disease or disorder is
[0149] a. an auto immune disease;
[0150] b. a cancer;
[0151] c. a muscular dystrophy;
[0152] d. a neuro-muscular disease;
[0153] e. a sugar or glycogen storage disease;
[0154] f. an expanded repeat disease;
[0155] g. a dominant negative disease;
[0156] h. a cardiomyopathy;
[0157] i. a viral disease;
[0158] j. a progeroid disease; or
[0159] k. any combination thereof.
[0160] In certain example embodiments, the expanded repeat disease is Huntington's disease, a Myotonic Dystrophy, or Facioscapulohumeral muscular dystrophy (FSHD).
[0161] In certain example embodiments, the muscular dystrophy is Duchene muscular dystrophy, Becker Muscular dystrophy, a Limb-Girdle muscular dystrophy, an Emery Dreifuss muscular dystrophy, a myotonic dystrophy, or FSHD.
[0162] In certain example embodiments, the myotonic dystrophy is Type 1 or Type 2.
[0163] In certain example embodiments, the cardiomyopathy is dilated cardiomyopathy, hypertrophic cardiomyopathy, DMD-associated cardiomyopathy, or Dannon disease.
[0164] In certain example embodiments, the sugar or glycogen storage disease is a MPS type III disease or Pompe disease.
[0165] In certain example embodiments, the MPS type III disease, is MPS Type IIIA, IIIB, IIIC, or IIID.
[0166] In certain example embodiments, the neuro-muscular disease is Charcot-Marie-Tooth disease or Friedreich's Ataxia.
[0167] These and other embodiments, objects, features, and advantages of the example embodiments will become apparent to those having ordinary skill in the art upon consideration of the following detailed description of illustrated example embodiments.BRIEF DESCRIPTION OF THE DRAWINGS
[0168] An understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention may be utilized, and the accompanying drawings of which:
[0169] FIG. 1 demonstrates the adeno-associated virus (AAV) transduction mechanism, which results in production of mRNA from the transgene.
[0170] FIG. 2 shows a graph that can demonstrate that mRNA-based selection of AAV variants can be more stringent than DNA-based selection. The virus library was expressed under the control of a CMV promoter.
[0171] FIGS. 3A-3B show graphs that can demonstrate a correlation between the virus library and vector genome DNA (FIG. 3A) and mRNA (FIG. 3B) in the liver.
[0172] FIGS. 4A-4F show graphs that can demonstrate capsid variants present at the DNA level and expressed at the mRNA level identified in different tissues. For this experiment, the virus library was expressed under the control of a CMV promoter.
[0173] FIGS. 5A-5C show graphs that can demonstrate capsid mRNA expression in different tissues under the control of cell-type specific promoters (as noted on x-axis). CMV was included as an exemplary constitutive promoter. CK8 is a muscle-specific promoter. MHCK7 is a muscle-specific promoter. hSyn is a neuron specific promoter. Expression levels from the cell type-specific promoters have been normalized based on expression levels from the constitutive CMV promoter in each tissue.
[0174] FIG. 6 shows a schematic demonstrating embodiments of a method of producing and selecting capsid variants for tissue-specific gene delivery across species.
[0175] FIG. 7 shows a schematic demonstrating embodiments of generating an AAV capsid variant library, particularly insertion of a random n-mer (n=3-15 amino acids) into a wild-type AAV, e.g. AAV9.
[0176] FIG. 8 shows a schematic demonstrating embodiments of generating an AAV capsid variant library, particularly variant AAV particle production. Each capsid variant encapsulates its own coding sequence as the vector genome.
[0177] FIG. 9 shows schematic vector maps of representative AAV capsid plasmid library vectors (see e.g. FIG. 8) that can be used in an AAV vector system to generate an AAV capsid variant library.
[0178] FIG. 10 shows a graph that can demonstrate the viral titer (calculated as AAV9 vector genome / 15 cm dish) produced by constructs containing different constitutive and cell-type specific mammalian promoters.
[0179] FIGS. 11A-11F show graphs that can demonstrate the results obtained after the first round of selection in C57BL / 6 mice using a capsid library expressed under the control of the MHCK7 muscle-specific promoter.
[0180] FIGS. 12A-12D show graphs that can demonstrate the results obtained after the second round of selection in C57BL / 6 mice using a capsid library expressed under the control of the MHCK7 muscle-specific promoter.
[0181] FIGS. 13A-13B shows graphs that can demonstrate a correlation between the abundance of variants encoded by synonymous codons.
[0182] FIG. 14 shows a graph that can demonstrate a correlation between the abundance of the same variants expressed under the control of two different muscle specific promoters (MHCK7 and CK8).
[0183] FIG. 15 shows a graph that can demonstrate muscle-tropic capsid variants that produce rAAV with similar titers to wild-type AAV9 capsid.
[0184] FIG. 16 shows images that can demonstrate a comparison of mouse tissue transduction between rAAV9-GFP and rMyoAAV-GFP.
[0185] FIG. 17 shows a panel of images that can demonstrate a comparison of mouse tissue transduction between rAAV9-GFP and rMyoAAV-G.
[0186] FIG. 18 shows a panel of images that can demonstrate a comparison of mouse tissue transduction between rAAV9-GFP and rMyoAAV-GF.
[0187] FIG. 19 shows a schematic of selection of potent capsid variants for muscle-directed gene delivery across species.
[0188] FIGS. 20A-20C show tables that can demonstrate selection in different strains of mice identifies the same variants as the top muscle-tropic hits.
[0189] FIG. 21 shows images that can demonstrate a comparison of mouse muscle transduction between rAAV9-GFP and rMyoAAV-GFP.
[0190] FIG. 22 shows graphs that can demonstrate a comparison of mouse tissue transduction between rAAV9-GFP and rMyoAAV-GFP.
[0191] FIG. 23 shows graphs that can demonstrate a comparison of vector genome biodistribution between rAAV9-GFP and rMyoAAV-GFP.
[0192] FIGS. 24A-24B show images that can demonstrate faster kinetics of in vivo gene expression in muscle by MyoAAV as compared to AAV9 and AAV8.
[0193] FIG. 25 can demonstrate a mechanism of correction of a DMD mutation in model mdx mice by MyoAAV-CRISPR as compared to AAV9-CRISPR.
[0194] FIGS. 26A-26C can demonstrate correction of a DMD mutation in model mdx mice with MyoAAV-CRISPR as compared to AAV9-CRISPR.
[0195] FIG. 27 can demonstrate that MyoAAV uses integrin heterodimers as the receptor to enter cells.
[0196] FIG. 28 shows graphs that can demonstrate that myoAAV can transduce both mouse and human primary myotubes 50-100 times more effectively than AAV9.
[0197] FIGS. 29A-29B can demonstrate that integrin alpha V small molecule inhibitors suppress transduction of human primary myotubes by MyoAAV.US_DESCRIPTION_OF_EMBODIMENTS
[0198] The figures herein are for illustrative purposes only and are not necessarily drawn to scale.DETAILED DESCRIPTION OF THE EXAMPLE EMBODIMENTSGeneral Definitions
[0199] Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. Definitions of common terms and techniques in molecular biology may be found in Molecular Cloning: A Laboratory Manual, 2nd edition (1989) (Sambrook, Fritsch, and Maniatis); Molecular Cloning: A Laboratory Manual, 4th edition (2012) (Green and Sambrook); Current Protocols in Molecular Biology (1987) (F. M. Ausubel et al. eds.); the series Methods in Enzymology (Academic Press, Inc.): PCR 2: A Practical Approach (1995) (M. J. MacPherson, B. D. Hames, and G. R. Taylor eds.): Antibodies, A Laboratory Manual (1988) (Harlow and Lane, eds.): Antibodies A Laboraotry Manual, 2nd edition 2013 (E. A. Greenfield ed.); Animal Cell Culture (1987) (R. I. Freshney, ed.); Benjamin Lewin, Genes IX, published by Jones and Bartlet, 2008 (ISBN 0763752223); Kendrew et al. (eds.), The Encyclopedia of Molecular Biology, published by Blackwell Science Ltd., 1994 (ISBN 0632021829); Robert A. Meyers (ed.), Molecular Biology and Biotechnology: a Comprehensive Desk Reference, published by VCH Publishers, Inc., 1995 (ISBN 9780471185710); Singleton et al., Dictionary of Microbiology and Molecular Biology 2nd ed., J. Wiley & Sons (New York, N.Y. 1994), March, Advanced Organic Chemistry Reactions, Mechanisms and Structure 4th ed., John Wiley & Sons (New York, N.Y. 1992); and Marten H. Hofker and Jan van Deursen, Transgenic Mouse Methods and Protocols, 2nd edition (2011).
[0200] As used herein, the singular forms “a”“an”, and “the” include both singular and plural referents unless the context clearly dictates otherwise.
[0201] The term “optional” or “optionally” means that the subsequent described event, circumstance or substituent may or may not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not.
[0202] The recitation of numerical ranges by endpoints includes all numbers and fractions subsumed within the respective ranges, as well as the recited endpoints. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms a further embodiment. For example, if the value “about 10” is disclosed, then “10” is also disclosed.
[0203] It is to be understood that such a range format is used for convenience and brevity, and thus, should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. To illustrate, a numerical range of “about 0.1% to 5%” should be interpreted to include not only the explicitly recited values of about 0.1% to about 5%, but also include individual values (e.g., about 1%, about 2%, about 3%, and about 4%) and the sub-ranges (e.g., about 0.5% to about 1.1%; about 5% to about 2.4%; about 0.5% to about 3.2%, and about 0.5% to about 4.4%, and other possible sub-ranges) within the indicated range. Where a range is expressed, a further embodiment includes from the one particular value and / or to the other particular value.
[0204] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the disclosure. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure. For example, where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure, e.g. the phrase “x to y” includes the range from ‘x’ to ‘y’ as well as the range greater than ‘x’ and less than ‘y’. The range can also be expressed as an upper limit, e.g. ‘about x, y, z, or less' and should be interpreted to include the specific ranges of ‘about x’, ‘about y’, and ‘about z’ as well as the ranges of ‘less than x’, ‘less than y’, and ‘less than z’. Likewise, the phrase ‘about x, y, z, or greater’ should be interpreted to include the specific ranges of ‘about x’, ‘about y’, and ‘about z’ as well as the ranges of ‘greater than x’, ‘greater than y’, and ‘greater than z’. In addition, the phrase “about ‘x’ to ‘y’”, where ‘x’ and ‘y’ are numerical values, includes “about ‘x’ to about ‘y’”.
[0205] The terms “about” or “approximately” as used herein when referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, are meant to encompass variations of and from the specified value, such as variations of + / −10% or less, + / −5% or less, + / −1% or less, and + / −0.1% or less of and from the specified value, insofar such variations are appropriate to perform in the disclosed invention. It is to be understood that the value to which the modifier “about” or “approximately” refers is itself also specifically, and preferably, disclosed. As used herein, the terms “about,”“approximate,”“at or about,” and “substantially” can mean that the amount or value in question can be the exact value or a value that provides equivalent results or effects as recited in the claims or taught herein. That is, it is understood that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but may be approximate and / or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art such that equivalent results or effects are obtained. In some circumstances, the value that provides equivalent results or effects cannot be reasonably determined. In general, an amount, size, formulation, parameter or other quantity or characteristic is “about,”“approximate,” or “at or about” whether or not expressly stated to be such. It is understood that where “about,”“approximate,” or “at or about” is used before a quantitative value, the parameter also includes the specific quantitative value itself, unless specifically stated otherwise.
[0206] As used herein, a “biological sample” may contain whole cells and / or live cells and / or cell debris. The biological sample may contain (or be derived from) a “bodily fluid”. The present invention encompasses embodiments wherein the bodily fluid is selected from amniotic fluid, aqueous humour, vitreous humour, bile, blood serum, breast milk, cerebrospinal fluid, cerumen (earwax), chyle, chyme, endolymph, perilymph, exudates, feces, female ejaculate, gastric acid, gastric juice, lymph, mucus (including nasal drainage and phlegm), pericardial fluid, peritoneal fluid, pleural fluid, pus, rheum, saliva, sebum (skin oil), semen, sputum, synovial fluid, sweat, tears, urine, vaginal secretion, vomit and mixtures of one or more thereof. Biological samples include cell cultures, bodily fluids, cell cultures from bodily fluids. Bodily fluids may be obtained from a mammal organism, for example by puncture, or other collecting or sampling procedures.
[0207] The terms “subject,”“individual,” and “patient” are used interchangeably herein to refer to a vertebrate, preferably a mammal, more preferably a human. Mammals include, but are not limited to, murines, simians, humans, farm animals, sport animals, and pets. Tissues, cells and their progeny of a biological entity obtained in vivo or cultured in vitro are also encompassed.
[0208] Various embodiments are described hereinafter. It should be noted that the specific embodiments are not intended as an exhaustive description or as a limitation to the broader embodiments discussed herein. One embodiment described in conjunction with a particular embodiment is not necessarily limited to that embodiment and can be practiced with any other embodiment(s). Reference throughout this specification to “one embodiment”, “an embodiment,”“an example embodiment,” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment,”“in an embodiment,” or “an example embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to a person skilled in the art from this disclosure, in one or more embodiments. Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention. For example, in the appended claims, any of the claimed embodiments can be used in any combination.
[0209] Reference is made to U.S. Provisional Application No. 62 / 899,453 and International Application No. PCT / US20 / 50534.
[0210] All publications, published patent documents, and patent applications cited herein are hereby incorporated by reference to the same extent as though each individual publication, published patent document, or patent application was specifically and individually indicated as being incorporated by reference.Overview
[0211] Embodiments disclosed herein provide muscle-specific targeting moieties that can be coupled to or otherwise associated with a cargo. Embodiments disclosed herein provide polypeptides and particles that can incorporate one or more of the muscle-specific targeting moieties. The polypeptides and / or particles can be coupled to, attached to, encapsulate, or otherwise incorporate a cargo, thereby associating the cargo with the targeting moiety(ies).
[0212] Embodiments disclosed herein provide muscle-specific targeting moieties that can contain one or more of an n-mer motif as further described herein, an RGD motif as further described herein, or both. In some embodiments, the n-mer motif and / or the RGD motif can confer muscle-specificity of the targeting moiety.
[0213] Embodiments disclosed herein provide engineered adeno-associated virus (AAV) capsids that can be engineered to confer cell-specific and / or species-specific tropism to an engineered AAV particle.
[0214] Embodiments disclosed herein also provide methods of generating the rAAVs having engineered capsids that can involve systematically directing the generation of diverse libraries of variants of modified surface structures, such as variant capsid proteins. Embodiments of the method of generating rAAVs having engineered capsids can also include stringent selection of capsid variants capable of targeting a specific cell, tissue, and / or organ type. Embodiments of the method of generating rAAVs having engineered capsids can include stringent selection of capsid variants capable of efficient and / or homogenous transduction in at least two or more species.
[0215] Embodiments disclosed herein provide vectors and systems thereof capable of producing an engineered AAV described herein.
[0216] Embodiments disclosed herein provide cells that can be capable of producing the engineered AAV particles described herein. In some embodiments, the cells include one or more vectors or system thereof described herein.
[0217] Embodiments disclosed herein provide engineered AAVs that can include an engineered capsid described herein. In some embodiments, the engineered AAV can include a cargo polynucleotide to be delivered to a cell. In some embodiments, the cargo polynucleotide is a gene modification polynucleotide.
[0218] Embodiments disclosed herein provide formulations that can contain an engineered AAV vector or system thereof, an engineered AAV capsid, engineered AAV particles including an engineered AAV capsid described herein, and / or an engineered cell described herein that contains an engineered AAV capsid, and / or an engineered AAV vector or system thereof. In some embodiments, the formulation can also include a pharmaceutically acceptable carrier. The formulations described herein can be delivered to a subject in need thereof or a cell.
[0219] Embodiments disclosed herein also provide kits that contain one or more of the one or more of the polypeptides, polynucleotides, vectors, engineered AAV capsids, engineered AAV particles, cells, or other components described herein and combinations thereof and pharmaceutical formulations described herein. In embodiments, one or more of the polypeptides, polynucleotides, vectors, engineered AAV capsids, engineered AAV particles cells, and combinations thereof described herein can be presented as a combination kit.
[0220] Embodiments disclosed herein provide methods of using the engineered AAVs having a cell-specific tropism described herein to deliver, for example, a therapeutic polynucleotide to a cell. In this way, the engineered AAVs described herein can be used to treat and / or prevent a disease in a subject in need thereof. Embodiments disclosed herein also provide methods of delivering the engineered AAV capsids, engineered AAV virus particles, engineered AAV vectors or systems thereof and / or formulations thereof to a cell. Also provided herein are methods of treating a subject in need thereof by delivering an engineered AAV particle, engineered AAV capsid, engineered AAV capsid vector or system thereof, an engineered cell, and / or formulation thereof to the subject.
[0221] Additional features and advantages of the embodiments engineered AAVs and methods of making and using the engineered AAVs are further described herein.Muscle-Specific Targeting Moieties and Compositions Thereof
[0222] Described herein are targeting moieties that are capable of specifically targeting, binding, associating with, or otherwise interact specifically with a muscle cell. N-mer motifs are short peptide motifs that can confer cell and / or tissue type-targeting capabilities to another molecule, such as a cargo, to which it is incorporated, coupled to, attached, or otherwise associated with. In one example embodiment, the n-mer motif is incorporated into a viral capsid such that it is expressed on the capsid surface and confers tissue-specific targeting capability to the viral particle to facilitate tissue-specific delivery of viral particle and any optional cargo contained therein. In certain example embodiments, the n-mer motif is about 1-20 amino acids, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids long. The term n-mer motif encompasses both n-mer motifs that have an RGD motif and those that do not (referred to herein as “non-RGD n-mer motifs”). In some example embodiments, the n-mer motif confers muscle cell / tissue specificity. In some example embodiments, the n-mer motif that confers muscle cell / tissue specificity is an RGD motif. In some example embodiments, the n-mer motif that confers muscle cell / tissue specificity is a non-RGD n-mer motif.
[0223] In some embodiments, the targeting moiety is or includes one or more n-mer motifs, where each of the one or more n-mer motifs is independently selected from an RGD motif or a non-RGD n-mer motif. N-mer motifs, RGD motifs and non-RGD n-mer motifs are described in greater detail elsewhere herein. In some embodiments, the targeting moiety includes more than one n-mer motifs, where each of the more than one n-mer motifs is independently selected from an RGD motif or a non-RGD n-mer motif. In some embodiments, the targeting moiety can include 1, 2, 3, 4, 5, 6, 7, 8, 9 10 or more n-mer motifs, where each n-mer motif is independently selected from an RGD motif or a non-RGD n-mer motif. In some embodiments, all the n-mer motifs included in the targeting moiety can be the same (i.e. have the same amino acid sequence). In some embodiments where more than one n-mer motif is included, at least two of the n-mer motifs are different from each other (i.e. have a different amino acid sequence). In some embodiments where more than one n-mer motif is included, all the n-mer motifs are different from each other. In some embodiments, each n-mer motif included in the targeting moiety can be any one of those set forth in any of Tables 1-6 and 8-9, which correspond to SEQ ID NOS: 13-50, 1277-2493, 3737-4979, 6647-8313, 8314-8502, or 8692-8889.TABLE 1CK8 Results mRNA Second Round of Capsid Variant Selection in C57BL6mice-score capped at 100Sum ofmusclemRNAVariantSEQ IDAmino AcidSEQ IDscore_cappedIDNucleotide SequenceNO:SequenceNO:at 1001AGGGGTGATCTTTCTACGCCT60RGDLSTP1277715.3662AGGGGCGACCTGAACCAATAC61RGDLNQY1278712.1493CGGGGTGATCTTACTACGCCT62RGDLTTP1279461.5364AGGGGGGATGCGACGGAGCTT63RGDATEL1280452.775CGGGGTGATCAGCTTTATCAT64RGDQLYH1281444.5056AGAGGCGACTTATCCACACCC65RGDLSTP1282411.6927CGTGGTGATGTGGCGGCTAAG66RGDVAAK1283371.78AGAGGAGACTTGACAACCCCA67RGDLTTP1284361.4869CGGGGTGATCTTAATCAGTAT68RGDLNQY1285342.71210CGAGGAGACACCATGAGCAAA69RGDTMSK1286325.63211CGCGGAGACGTAGCCGCCAAA70RGDVAAK1287315.0112CGGGGGGATACTATGTCTAAG71RGDTMSK1288309.56713CGGGGTGACGCAACAGAATTG72RGDATEL1289306.9914GCACGGTCAAACGACTCGGTC73ARSNDSV1290293.2215CGGGGTGACATGAACAACTCA74RGDMNNS1291268.67716ACGATGGGTGCTAATGGTACT75TMGANGT1292260.85317CCTAATGTTACGCAGTCTTAT76PNVTQSY1293259.71818CGTTTGGACCTGCAAGTCCAC77RLDLQVH1294257.6519GGGCTTTCTAAGGCGTCTGAT78GLSKASD1295255.93820GATCCTGGTCGGACGGGTACG79DPGRTGT1296253.32521TATCGGGGTAGGGAGGATTGG80YRGREDW1297244.8322AGATACGGAGAATCCATCGAA81RYGESIE1298231.69623AGTCTGAACAACATGGGATCG82SLNNMGS1299229.604424AATAGTGATCAGCGGAATTGG83NSDQRNW1300229.03125CGTGGTGATATGTCTCGTGAG84RGDMSRE1301227.08126ATGACTGATGCGAATAGGATT85MTDANRI1302226.19427GTCTACAACGGCAACGTAGTA86VYNGNVV1303223.66328CGTGGGGATATGATTAATACG87RGDMINT1304223.4629AGTGGTCTTTCGCATGGTCAG88SGLSHGQ1305221.72630ACTGGCCAATTAGTAGGAACC89TGQLVGT1306221.18131GCTAATTCTATTGGGGGTCCG90ANSIGGP1307220.30432TACAGTCAATCGCTGTCTGAA91YSQSLSE1308220.0233TATCATAAGTATAGTACGGAT92YHKYSTD1309217.6434GCTCGTCATGATGAGCATGTG93ARHDEHV131021735GCCATAGACTCTATCAAACAA94AIDSIKQ1311216.07136CGTTTGGACCTGCAAGTCAAC95RLDLQVN131221537CGCGGCGACATGATAAACACC96RGDMINT1313214.27138AGTGTGTTGTCTCAGGCTAAT97SVLSQAN1314213.90739TTTACGGTGAATCAGGATCTT98FTVNQDL1315213.7840ACGGATAATGGTCTTCTTGTG99TDNGLLV1316211.78741TATCAGCAGACTTCTAGTACG100YQQTSST1317211.38642ACAGAACAATCTTACTCACGA101TEQSYSR1318210.76243ATTATGGGGCTTAGTCAGGCT102IMGLSQA1319208.15744GCTACTGCGCATCAGGATGGT103ATAHQDG1320207.21245TATAATGCTACTCCTTCGCAG104YNATPSQ1321206.96446TATACGCAGGGTATTATGAAT105YTQGIMN1322206.67247GAATCCCTCCCAATCTCTAAA106ESLPISK1323206.57648GGCACCGTCGTTCCGGGCTCC107GTVVPGS1324206.11149GGATTAGCTAGTCTACACCTG108GLASLHL1325204.39450TATATTGCTGCGGGTGAGCAG109YIAAGEQ1326204.2451AACACCTACCCCTTCAACGCC110NTYPFNA1327203.93152GTTGGTGCGAGTACGGCTTCG111VGASTAS1328202.9253GGATCCAACTACTTAGCAAAC112GSNYLAN1329202.85754GATACTGGTCGGACGGGTACG113DTGRTGT1330202.8355AAGCCGAATACGATGAGTGAT114KPNTMSD1331202.728256GTAGACAAATCTAGCCCAGTG115VDKSSPV1332201.84957AGTTCGGACCCAAAAGGTCAA116SSDPKGQ1333201.82558TGGCAGACGAATGGTATGCAG117WQTNGMQ1334201.694359ACCGGTAGCTTGAACTCTATG118TGSLNSM1335201.67160CATTCTAATTCGAGTCAGAAT119HSNSSQN1336200.95461GGCCGTGACGACCTCACAAAC120GRDDLTN1337200.91162GATACTTATAAGGGTAAGTGG121DTYKGKW1338200.778763TATACGGCGCAGACCGGCTGG122YTAQTGW133920064AATCAGGTGGGTGCGTCTGCG123NQVGASA134020065ATCGACGTACTGAACGGAAGT124IDVLNGS134120066TTTCGGACGGTGTATACTGGT125FRTVYTG134220067GGAAACATGGTGACTCCAAAC126GNMVTPN134320068GATACTTATAACGGTAAGTGG127DTYNGKW134420069ACCATCCAAGACCACATAAAA128TIQDHIK134520070GGAGCAAAAGGAACCATGGGC129GAKGTMG134620071ACGAGGAGCAACTCCGACGAA130TRSNSDE134720072GCTACTACTCTTACTGGTGAT131ATTLTGD134820073TCATACGGAGGATCTGGCCCC132SYGGSGP1349198.71574GAAAAATCCGTCGAATCCAAA133EKSVESK1350196.41875CGAGGCGACACAATGAACTAC134RGDTMNY1351195.308276CGGGATCTGGGGCAGACCGGC135RDLGQTG1352194.3477AGTCCGCAGCTGAGTGTGATG136SPQLSVM1353194.2178CGAGGAGACAACAGCACACCG137RGDNSTP1354193.0579CCTATGGCAGGACACCCCCCG138PMAGHPP1355192.72680ACGGCGTATCAGGCTGGTCTG139TAYQAGL1356191.77881GTGGTAAACCAAGGAAACCAA140VVNQGNQ1357191.73782GATAAGACTGAGATGCTGCAG141DKTEMLQ1358191.1383ACTGTGATGATGAGTACGAGG142TVMMSTR1359191.06384CAGCAGAATACGCGTTTGCCG143QQNTRLP1360190.182585TACCAACACAACCAAGCCCAC144YQHNQAH1361189.59586AATCAGAGTATTAATAATATT145NQSINNI1362188.65487CGAGGAGACCACAGCACACCG146RGDHSTP1363187.36588GACTCTACACTTCACTTAAGT147DSTLHLS1364187.3689GCGAACATAGAAAACACGTCA148ANIENTS1365187.0390ACAAACGCTGCTCTAGTACCA149TNAALVP1366185.974391GGGCAGAAGGAGACTACTGCG150GQKETTA1367184.45792GAACTTAACACCGCACACGCA151ELNTAHA1368184.05993GGTGTTAGTAGTAATTCTGCG152GVSSNSA1369183.96494AGCACAAACGCGGGACAAAGG153STNAGQR1370183.57195GAACAACAAAAAACAGACAAC154EQQKTDN1371182.33196GCTGTTGTGAATGAGAATATG155AVVNENM1372182.397GGCAGCGTCAGCACCAGCGCA156GSVSTSA1373181.45198GAGTTGGGTAGTCAGCGTATG157ELGSQRM1374181.3699AGAGGCGACTTATCCACACAC158RGDLSTH1375181.15100GACCACCAACAAGCCCTAGCT159DHQQALA1376180.295101AACAGATCTGACGCTCACGAA160NRSDAHE1377180.265102AATGTTAATGCGCAGAGTAGG161NVNAQSR1378179.918103ACCCAAGGGAACAACATGGTA162TQGNNMV1379179.575104ACGGCGCTGAATACGTATCCT163TALNTYP1380179.568105GTCTCTACATACCTCCTGGCA164VSTYLLA1381179.172106GGCGGCAACTACAACACAACT165GGNYNTT1382178.62107AGTAATATTAAGCCGGAGATT166SNIKPEI1383178.567108CCGAGGGTGCATGGTCAGGTT167PRVHGQV1384178.479109TCTAATTCTAATACTGCTGCT168SNSNTAA1385178.119110CTTGAGGTGGCGACGAGTCCG169LEVATSP1386177.75111CACGACGCCGACAAATTAGCT170HDADKLA1387177.05112GGTGTGTATATTGATGGTCGG171GVYIDGR1388176.229113TCGATGCAGTCGTATACGATG172SMQSYTM1389175.538114TCTAAAGGAAACGAACAAATG173SKGNEQM1390175.311115GGTCGGGATTATGCTATGAGT174GRDYAMS1391174.17116ACTGATGGTATTTTTCAGCCT175TDGIFQP1392174.014117GGGAGCCCAGTGATAGTAAAC176GSPVIVN1393173.652118ACATTAACAGACGTTCACCGA177TLTDVHR1394172.837119AAAAGCGAAGTACCCGCCCGA178KSEVPAR1395172.72120GTCAACACTGGCGCACTCTTG179VNTGALL1396172.648121AGTCAGCAGGGTTTTACTCTG180SQQGFTL1397172.124122AATAATAAGTCTGTGCCGGAT181NNKSVPD1398172.0753123AGTGTGATGGTGGGTACGAAT182SVMVGTN1399171.86124CGAAACGAAAACACTTACAAC183RNENTYN1400170.674125CAAGCTAACTTATCAATAATC184QANLSII1401170.5862126CCCGGACGGGACAGCAGAACG185PGRDSRT1402169.875127TTTCCGGCTAATGGTGGTGCT186FPANGGA1403169.639128GCTGGTAAGGATCTTAGTAAT187AGKDLSN1404169.592129GCACAATTCGAATCAGGCCGA188AQFESGR1405169.281130GGATACGGCAGTTACAGCAAC189GYGSYSN1406169.247131ACAATCGTTTCCGCTTACGCC190TIVSAYA1407168.87132AATGTGAGTCCTAATTTGACT191NVSPNLT1408168.739133AGAGGCGACTTATCAACACCC192RGDLSTP1409167.66134TTCTTAGAAGGAGTCGCTCAA193FLEGVAQ1410167.647135GGCTCCGAACGAGGAGAACGA194GSERGER1411167.585136TTGAATGTTGGTTCGAGTCTT195LNVGSSL1412167.104137CGTATTGTGGCTAATGAGCAG196RIVANEQ1413166.96138CAATCTATCGGCCACCCCGTT197QSIGHPV1414166.7759139GGTGGTATGTCGGCGCATTCG198GGMSAHS1415166.775140CATTCTACGACGTCTATGACG199HSTTSMT1416166.711141ACTGTAAACGGTACGAACGTA200TVNGTNV1417166.64142CTTGCGCCTGATAATATTGGG201LAPDNIG1418166.005143CAAACAGCGACTCTCGTGGCA202QTATLVA1419165.921144GCATCAGCACCGTCTGAATTC203ASAPSEF1420165.64145TCGATGGAGGGTCAGCAGCAT204SMEGQQH1421165.62146CAAGACGTAGGACGCACGAAC205QDVGRTN1422164.147147GTCTACAACGGCAACGAAGTA206VYNGNEV1423164.11148GCACAGGCGCAGACAGGCTGG207AQAQTGW1424163.93149CGGCTGGATCTGACGCATACG208RLDLTHT1425163.75150GCTGCACACGGCCGCGAACAA209AAHGREQ1426163.577151AGAGGCGACTTATACACACCC210RGDLYTP1427163.43152GGTATGCAGCAGAGGGAGAAG211GMQQREK1428163.075153CAGACTCAGGCGAGTACTAAT212QTQASTN1429161.336154CGGGACACCAACGCCCTCGGA213RDTNALG1430161.225155TCGAGTCAGATTTCTAATAGT214SSQISNS1431161.063156CAGTCGGTTAATAGTACGAGT215QSVNSTS1432160.873157GCTCTGGAGAGGGCTCAGTAT216ALERAQY1433160.837158CATACTGGGCATAGTTCTGTG217HTGHSSV1434160.068159CGGGGAGACATGACCCGAGCA218RGDMTRA1435159.605160TTTCAGCGTGATCTTGGGCAT219FQRDLGH1436159.442161ACAACCGGCGACATAATACGC220TTGDIIR1437159.11162TCTTTTCAGACGGATCGTGCG221SFQTDRA1438159.04163CAATCCAGCGACGGCCGAGTG222QSSDGRV1439158.634164ACTTCTGGGGCTTTGACCCGG223TSGALTR1440158.32165AATTCGAATACTGTGAATACG224NSNTVNT1441157.71166ATCTCCGGTAGTAGCAGTCTA225ISGSSSL1442157.64167AACGACAAATCAACCAACGTA226NDKSTNV1443157.594168ATCGTACTTGCTCCCACATCG227IVLAPTS1444157.48169TCAGGCGTCAACTACGGTGTC228SGVNYGV1445157.321170GTCGGCGCCCAACGGGACCCC229VGAQRDP1446157.055171ACGGGTATGAATAGTAATAAG230TGMNSNK1447156.85172ATCGAAGCCTACTCACGAGAC231IEAYSRD1448156.774173TTACACACAACACTAATGCCC232LHTTLMF1449156.364174TCTGATAATCATCTGAAGACT233SDNHLKT1450156.334175CGAAACGAAGACAAAGGAGGA234RNEDKGG1451156.027176ACGAAGGGTGCTAATGGTACT235TKGANGT1452155.56177GTCTACAACGGCAACGTAGAA236VYNGNVE1453155.56178TCAAACAGCGGAGGCAACCAC237SNSGGNH1454155.294179GTAGCCGCGGGACCAGAAGCG238VAAGPEA1455154.25180ACGTCTCTTAGTGGTAGTGCG239TSLSGSA1456153.988181GTTGGGCTGCAGAGTAATACT240VGLQSNT1457153.453182CACACCGCCCACAGCGTGGAC241HTAHSVD1458153.3866183AACGTGGGAATGAGCTCAACC242NVGMSST1459153.212184CATGCGGATGTGAATGCTGGG243HADVNAG1460153.21185AAAGCGGGACAACTAGTGGAA244KAGQLVE1461153.178186AGTACTTTTAGTGTGCTGCCT245STFSVLP1462153.09187CCTCAGTCTCCGAGTCGGGTT246PQSPSRV1463152.823188CACACCGCCACCCTTAGCAGC247HTATLSS1464152.8189CTTCCGCGTCATGATCAGTAT248LPRHDQY1465152.412190CAAGTGAACAACCCACTCACA249QVNNPLT1466151.574191ACAACAGAAACCGCACGAGGT250TTETARG1467151.4255192GTTCATGGGACGTTGACTTAT251VHGTLTY1468150.654193TATAGTACTGATCTTAGGATG252YSTDLRM1469150.626194GCACACGCTACCTCAAGCACT253AHATSST1470150.587195AGGGAGAGTGCTGCTCTGGCG254RESAALA1471150.506196AAGGATACTAATCAGCAGATT255KDTNQQI1472150.189197AGTATGCAATCATACACCATG256SMQSYTM1473148.994198ACAGCCTACTCGCCCACAGTC257TAYSPTV1474148.946199GAATCTGCCCACCAAAGAATA258ESAHQRI1475148.867200AGATACACAACAGCACAACAA259RYTTAQQ1476148.802201ACGTCTGTGGCGAATGTGAGT260TSVANVS1477148.731202AGGGATCAGCATACTTCTATT261RDQHTSI1478148.687203TCTGTTACGTCTTCTGGTCCG262SVTSSGP1479148.574204GCGGTTGTTCTGAATAGTAAT263AVVLNSN1480148.476205CCTGGGAATCCGTCTAGTAAT264PGNPSSN1481147.792206ACGGGGTCTACTACTCAGCTT265TGSTTQL1482147.767207GCTAATGAGCATAATGTGGGT266ANEHNVG1483147.569208ATGCAAAGAGAAGCAGCCAAC267MQREAAN1484147.562209TTAACCGACACAAACACCCGG268LTDTNTR1485147.306210CGAATGACCGAAATATCATAC269RMTEISY1486146.933211AAAGTGGACATGACCTCCAAA270KVDMTSK1487146.392212AGAGGAGACTTATCCACACCC271RGDLSTP1488146.3213CAAGCAAAAGCTAGCACAACT272QAKASTT1489146.214214CTACCCTCAACAGAAACTTTG273LPSTETL1490145.892215AGTAGTGCGCTTAATGCGTAT274SSALNAY1491145.667216TCGTCTGATCCTAAGGGGCAG275SSDPKGQ1492145.644217TTAGACGTGACGAGAATGAGA276LDVTRMR1493145.51218GCGGATGGTGGTGATAAGGGG277ADGGDKG1494145.45219ATGCTGTCTCAGGTTACGTTG278MLSQVTL1495145.32220AGTGTTAGTTCTGTGGTGTTG279SVSSVVL1496145.202221ACCGAATCGCAAACCATGAGG280TESQTMR1497145.0149222TTCGGATCCCAAGAAAAACTC281FGSQEKL1498144.467223ACAGCCGGCGGCGAACGCGCC282TAGGERA1499144.445224GATCATAGTAAGCAGAGTTCG283DHSKQSS1500144.0179225ATTGATAGTACTTGGAATACG284IDSTWNT1501143.92226TCGCCTCGCCCCGAACTCCGA285SPRPELR1502143.362227AGTATTGCGACTGCTACTAGT286SIATATS1503143.312228GTAATAGGCGGACACGGGACT287VIGGHGT1504143.136229AGCACCGCCATGTACCCCCAC288STAMYPH1505142.798230CGGGACTTGAGACCCGTGACG289RDLRPVT1506142.461231GCTCATCTGACTGATCTTCCG290AHLTDLP1507142.37232TTTCTGAATAGTACGCAGCTT291FLNSTQL1508142.276233TTAAACAACAGTGCCACAGTC292LNNSATV1509142.021234GATCGTCCGAATAATATGACG293DRPNNMT1510141.945235TCATCGTCAGACTCACCCAGA294SSSDSPR1511141.849236CGCTTGGACGTTGGAAGCCCG295RLDVGSP1512141.82237GCGCAGCAGAGTCTTCATGGT296AQQSLHG1513141.401238ATGGGGAAGCATGAGGGTCTT297MGKHEGL1514141.2916239GAGAATGCTCGTGAGGGTGTG298ENAREGV1515140.87240ACCGTATCTCTCTCGGAAGGC299TVSLSEG1516140.529241CTTAACACACTAATCGACCGG300LNTLIDR1517140.256242GAACTCTCCGTTCCGAAACCA301ELSVPKP1518140.203243AAAGACAAAAACGTATACATA302KDKNVYI1519140.171244AATGCGAATGGGCCTGTGAGT303NANGPVS1520140.158245CTTACTACGAATGGTATGCTG304LTTNGML1521140.147246GCCGGCGAATCTTCACCCACA305AGESSPT1522139.95247AGTGGGATTGGTACTTATTCT306SGIGTYS1523139.76248GTCAGATCTATGGACGAATTG307VRSMDEL1524139.74249ATGAACACCGGCTCTTCGAGT308MNTGSSS1525139.328250GGGGTGACTGTTAGGGAGCTT309GVTVREL1526139.099251CAGATTTTGAATTATAGTGTG310QILNYSV1527138.991252ATGGCGGGTGAGTATAGGGTT311MAGEYRV1528138.933253TGGTCGCATGATCGGCCTACT312WSHDRPT1529138.703254TGCAAAAACAACTCAGAATGC313CKNNSEC1530138.668255TTGACGACGAATAGTCATTAT314LTTNSHY1531138.525256ATGCTTGTTCAGAATACTCCT315MLVQNTP1532138.3257CGTGGTGCGACTGAGCATGCG316RGATEHA1533138.186258GCTTCGAATGGGAGTATGGGT317ASNGSMG1534138.1181259AATAGTTATACTGCTGGGAAG318NSYTAGK1535137.4033260TCCACCCAAGGAGCCATCCTC319STQGAIL1536137.294261TGGAATACGAATATGGCGATT320WNTNMAI1537137.17262GTCTCATCGTACGAAAAAATA321VSSYEKI1538137.055263GTGCTGAGTACGGGGCAGCGG322VLSTGQR1539136.9001264CCTATACCCCACGGTTCATCC323PIPHGSS1540136.523265AACGTGTCACTAACGCAAACG324NVSLTQT1541136.4003266TCTACCATCGGCAACAGCACG325STIGNST1542136.393267TCTGAGAAGCTGACTGATAAG326SEKLTDK1543136.36268TCCAAAGACTCGAACATAAGT327SKDSNIS1544136.166269GCGAATAGTAATCATGAGCGT328ANSNHER1545136.102270AGGGATACGGGTGATAAGGCT329RDTGDKA1546135.913271AGAACAGACACGCCGTCAACC330RTDTPST1547135.583272CCTACTATGTCGAGTCTGAAT331PTMSSLN1548135.539273GATATTACTAATCAGTCGTAT332DITNQSY1549135.473274CTTGTAAAACCGGAAACTTGG333LVKPETW1550134.988275GGGACTTCCTTGGAAAACCGA334GTSLENR1551134.981276GCTGCTGGTAATCCTACTCGT335AAGNPTR1552134.779277CACAACGTCGGCCTAGGACAC336HNVGLGH1553134.677278GTATCAACGACAACGGACCGG337VSTTTDR1554134.639279TATTTGTCGTCTGGTAAGATG338YLSSGKM1555134.553280GATAGTCGGAATGCTGCTTTG339DSRNAAL1556134.213281GTGGAGCGGAATACTGATATG340VERNTDM1557133.962282ACTGTTGGGAGTAATTCTATT341TVGSNSI1558133.95283GTGCGGTCTGGTAATAAGCCG342VRSGNKP1559133.87284GGCAGTTCGGGGAACAGCGGA343GSSGNSG1560133.776285TCTACTTCAATAGGAGTGGTA344STSIGVV1561133.69286CCGAGTCAGAGTAGGTCGCTT345PSQSRSL1562133.6751287CGGAATGAGAATCTTAATAAT346RNENLNN1563133.26288TCGTTGGGTAAGAGGGAGGAG347SLGKREE1564133.032289TCACGCTTGGACTCGAGCTCC348SRLDSSS1565132.783290GATTCGACGTATGTTTTGGCT349DSTYVLA1566132.54291GAGCGTAATCCTATTTCTGAT350ERNPISD1567132.49292GTTAGCTCCGGCCACACGAAA351VSSGHTK1568132.466293AAGTATACGGAGTCGAATGCG352KYTESNA1569132.305294AACCGCAACTCAGTTGGGACT353NRNSVGT1570132.2576295CACGAAAGCCACTACGTGTCA354HESHYVS1571132.014296ACGACTGGGGGGACGGGGATG355TTGGTGM1572131.954297GCGACTGATAAGATGACTCCT356ATDKMTP1573131.931298TCCGCGTCTAGCGGCGCTACA357SASSGAT1574131.886299TCAACCACTACTGGCCACATG358STTTGHM1575131.581300ATAATAGCATCCTCTACCACG359IIASSTT1576131.506301GATACTGGGTCTAGGATTGCG360DTGSRIA1577131.486302TGGGCTGATGATTCGCAGCGG361WADDSQR1578131.47303AGGGGTAACACTCTCGAAATG362RGNTLEM1579131.381304AATCTGCAGGTGAATGCGAAT363NLQVNAN1580131.172305GCGACGACTCAGCTGATGACT364ATTQLMT1581130.96306GCTGATACGAATATTATTGTG365ADTNIIV1582130.47307GCCATAACAATCACTCAAAAA366AITITQK1583130.225308GACTCCAACAAAGGAGCGACG367DSNKGAT1584130.1749309GGCAACGCTTCCGGAAACCCA368GNASGNP1585129.97310ACGATGGGTGCTAAAGGTACT369TMGAKGT1586129.92311TATCTGCAGACGGGTACTCTG370YLQTGTL1587129.907312GCATTACACACCAAAGACCTA371ALHTKDL1588129.846313GTCGACAAAAGCGAAGCCGTC372VDKSEAV1589129.734314GGGAGGACGGATCTTATGGCG373GRTDLMA1590129.651315GGCACGGAACCGCGCACTGCA374GTEPRTA1591129.37316AGAGGCGACATGTCACGAGAA375RGDMSRE1592129.137317CGGGGGGATACTAAGTCTAAG376RGDTKSK1593128.94318GGGACATTAGCCTCAATGTCC377GTLASMS1594128.734319CAGAAGTCTGTGACGTATTCG378QKSVTYS1595128.602320AGTACGGGGCAGACTCTTGTT379STGQTLV1596128.1669321TCGCACATAAACATGGGGTCG380SHINMGS1597128.101322GCGTTGAATGGTACTGGTAAT381ALNGTGN1598128.045323ACTACGAGTTCGAATCAGCAT382TTSSNQH1599128.003324AAAAACTACGCAAGCACCGAC383KNYASTD1600127.84325GAATCCACAAGCAGGACGTAC384ESTSRTY1601127.765326CCGCGTTCTATTACGGAGTTG385PRSITEL1602127.623327TACATAGCCGGAGGAGAAAAA386YIAGGEK1603127.544328ACTAGTAATTATATGCATGAG387TSNYMBE1604127.522329TTGGATCCTAATAGTACTCGG388LDPNSTR1605127.175330CACAGTGACATGGGCTCAAGC389HSDMGSS1606127.01331GACACCGCCAACCGATCCACA390DTANRST1607127.01332AACGCCGGACACAGCGGTCAA391NAGHSGQ1608126.611333AGTTTGGGGTCGGATCGTATG392SLGSDRM1609126.579334GACAACCAACAAGCCCTAGCT393DNQQALA1610126.49335CCATCCTCAGCGGGTAGCACA394PSSAGST1611126.201336GACAGGAAAGGGTACGACGCA395DRKGYDA1612126.06337GGAGGAAACCAAAACCTTACT396GGNQNLT1613125.7806338GTGAATCTGAATGAGACGGAG397VNLNETE1614125.719339TCCCCCGGCAACGGGTTGCTA398SPGNGLL1615125.687340TCTGTCGGGGACCTCACAAAA399SVGDLTK1616125.627341CGATACGAATCCGTCGGACTC400RYESVGL1617125.54342ACGAGAGAATTGACAAAAAAC401TRELTKN1618125.47343ACTCCAACTAACGGGAACCCT402TPTNGNP1619125.37344GCGACTGATCAGCGTTCGAGG403ATDQRSR1620125.26345GGAACATCGGCAGAATCACGC404GTSAESR1621125.214346AGGATGCTCTCTACTTTGCCT405RMLSTLP1622125.088347GGTATCAACTCCTCACACTTC406GINSSHF1623125.044348AGTAGCTCAACTGAAGGGCAA407SSSTEGQ1624124.971349GACAAACAACAAACCGGACAA408DKQQTGQ1625124.923350ACCCAACACCTACCATCCACA409TQHLPST1626124.773351GGTCTGGGGCAGCCTCAGTTG410GLGQPQL1627124.752352GTGACTAATGAGAGTCGTGCT411VTNESRA1628124.728353GGCAACTCGAACTACCGAGAA412GNSNYRE1629124.482354TGGAATGCTGAGAATAGTAAG413WNAENSK1630124.373355CCTGGGAGTCAGCGTCAGGAT414PGSQRQD1631124.325356CATACGTATTCGCAGGCTGAT415HTYSQAD1632124.3357ACTGCCGGCAACCTAAGAAGT416TAGNLRS1633124.203358GGCAGACACCTTCAATCGGAC417GRHLQSD1634124.19359AACAACGCACACACCGCCACT418NNAHTAT1635124.118360AGTACGAGTCAGGAGAATAGG419STSQENR1636124.0658361AGGGGTGATACTATGAATTAT420RGDTMNY1637124.04362CCGGTTGCTACTCAGCATGCG421PVATQHA1638123.9189363GGGCATTTGAATGCTCCGACT422GHLNAPT1639123.495364CAAATATTAAACTACTCAGTC423QILNYSV1640123.4365CAAAACCACGCGTCTGGTGAA424QNHASGE1641123.372366GGTTTAACAGGGCGGGAACTA425GLTGREL1642123.32367GACGTAGCCGTGACTCAACAC426DVAVTQH1643123.31368GCAACTTACACCGGGCGAACA427ATYTGRT1644123.292369AAAGAACTACAATGGCAACGA428KELQWQR1645123.251370GCTAGTTATAGTAGTATGGTG429ASYSSMV1646123.193371GTTATTAGTCATGGGGCGCTG430VISHGAL1647123.094372CCTATACACCACGGTTCATCC431PIHHGSS1648123.09373GTGGATAAGAATCATCCTTTG432VDKNHPL1649123.04374ACCTCGGGTGACCGGTACACG433TSGDRYT1650122.844375GGGACAAAAAGCTGGCCTGTC434GTKSWPV1651122.8432376TACAACGCCCACGAATCATTC435YNAHESF1652122.813377AGAGTCCACGACACTCCTTCA436RVHDTPS1653122.7503378GCACAAATCGAATCAGGCCGA437AQIESGR1654122.66379TGGAAGGATAATATGCGGATG438WKDNMRM1655122.624380ATGCCTAGTGAACCACCAGGG439MPSEPPG1656122.51381CGTGGTGATTATCCGACGTCG440RGDYPTS1657122.487382TTTCATAATGAGTCTTATGGG441FHNESYG1658122.36383TTGAATACGATGATTGATAAG442LNTMIDK1659122.272384TCCACACTAAGCCAAGGAGCA443STLSQGA1660122.2662385CCTTTGCACAACATACCTCCT444PLHNIPP1661122.24386GCTTCGTCTACGTTTTTGCCT445ASSTFLP1662122.24387ATGGAAGGAATGGGACTCGGA446MEGMGLG1663122.04388AAGGATTATAAGCCGTATGCT447KDYKPYA1664121.95389AATTTGCAGTCTGGTGTTCAG448NLQSGVQ1665121.91390ACAACTCTTAGCCAACAAAGC449TTLSQQS1666121.82391CTTATGTCGTCTACTTCCTCA450LMSSTSS1667121.536392ACTGGCCAAGGATTCTCGGCA451TGQGFSA1668121.45393TCTACAATCGGCAACAGCACG452STIGNST1669121.27394CTGAGGGCGAGTGAGGCTCCG453LRASEAP1670121.2297395CAGCCTAATAATGGTAATCAT454QPNNGNH1671121.02396TCGTCAGACGTTACCAGACAA455SSDVTRQ1672120.98397CGGGGTGACGCAACAGAAATG456RGDATEM1673120.74398TATAGGGGTAGGGAGGATTGG457YRGREDW1674120.58399AGCTTGCAACAATCACAATTG458SLQQSQL1675120.491400AAGCCGACTGCGAATGATTGG459KPTANDW1676120.3784401CGTCTGACTGATACTATGCAT460RLTDTMH1677120.35402CTTCATGGGAATTATAGTCCG461LHGNYSP1678120.346403ATTCCGGTTGGGGCGATGGCT462IPVGAMA1679120.248404CCGAACACCGCCTCAAACTTC463PNTASNF1680120.24405ACGAGTAGAGAAGTCAAAGGG464TSREVKG1681120.171406GACACGTCCTCCGGCAACAGG465DTSSGNR1682119.94407GAAGCAGTAACAAGTAAATGG466EAVTSKW1683119.919408CTAATCACAGCCACCACTAAC467LITATTN1684119.872409GATGGGGGTCGTTCGGGTATT468DGGRSGI1685119.847410TTCATGGAAGTCATGAAAAAC469FMEVMKN1686119.82411TCCTACCAAAACCCACCACCA470SYQNPPP1687119.701412ACTAATGTGACGTTTAAGCTT471TNVTFKL1688119.681413ATTTCTACGCATACGATGACG472ISTHTMT1689119.64414GAAACCCAAGGAGCAAGATAC473ETQGARY1690119.591415GCGGCTTATGAGCATGCGCCT474AAYEHAP1691119.588416TCAACGAACGACCGTGCGTTA475STNDRAL1692119.57417TTCACCGAACGCGCACTCCAA476FTERALQ1693119.423418GTAGCGGGCTTAGTCGACATA477VAGLVDI1694119.41419AGCTCGGTAACTAACCTTGCA478SSVTNLA1695119.38420GATACTACTACTGGTCATCTT479DTTTGHL1696119.27421ACGCGTAATTTGTCTGAGAGT480TRNLSES1697118.919422CAGGTGAATGTTGGGCCTGGT481QVNVGPG1698118.831423AAACAAACGATGTCCGACACA482KQTMSDT1699118.829424ATGTCGACAACCAGCAAAACT483MSTTSKT1700118.7215425ACTACAATAGGGACAAACCAA484TTIGTNQ1701118.676426GGGACTCTGACGCCGAATCTT485GTLTPNL1702118.622427TTTGATAGTTATAATATTGTG486FDSYNIV1703118.51428CGTGGTGCGCCTGAGCAAGCG487RGAPEQA1704118.47429ATCGAAAACGTAAACCACTTG488IENVNHL1705118.42430AGGTCTCTGGAGAGTCAGGCT489RSLESQA1706118.231431CAGTATACGAGTCTGAGTCCG490QYTSLSP1707118.006432ACGAAGGGTTATAATGATCTT491TKGYNDL1708117.876433GTCGCCTCGATGGTACACAAC492VASMVHN1709117.874434TCCACAACCCACACCTCAGCA493STTHTSA1710117.821435CTTGCGCACCCACAACCAAAC494LAHPQPN1711117.542436TCGATAAACAACATAGGCGCA495SINNIGA1712117.538437GCTATAGACTCCATCAAAATG496AIDSIKM1713117.472438TCTATGTATGGGCAGGCTGGG497SMYGQAG1714117.362439GAGTATGCTAATGCTAAGACT498EYANAKT1715117.351440TATCGGGCTTCGGATGTGGCG499YRASDVA1716117.348441GTTAGTTTGGAGAGTCGGTTG500VSLESRL1717117.332442ATTGAGACTAGTTCGCGTTCG501IETSSRS1718117.176443ATGGGAGTGAAACCCGAACAA502MGVKPEQ1719116.975444GCGCTTCCGTCTCGTGAGCGG503ALPSRER1720116.914445GGCACCGGATCTTCAGCGCAC504GTGSSAH1721116.896446CAAACGAACACCAACGACAGA505QTNTNDR1722116.664447GTATTACACTCTGTATCAGCA506VLHSVSA1723116.583448CCTTATTCTGCTACTGATCGG507PYSATDR1724116.577449GCAAACTCCGGATTACACAAC508ANSGLHN1725116.505450TATGAGAGTACTCATGTTAAT509YESTHVN1726116.418451AACAACGCACTAGTAGGAAGT510NNALVGS1727116.34452GGTATCAACTCCTCACACATC511GINSSHI1728116.28453AGTATTTCTGATAAGAATCAG512SISDKNQ1729116.141454GACCACCAACAAGCCCTAGCA513DHQQALA1730116.13455GACTCTACCAAAGCCATGCAA514DSTKAMQ1731116.116456ACTATTACTAGTCAGTCGGTG515TITSQSV1732115.95457GGCGCCCGTACAATCTTAGAC516GARTILD1733115.938458GAGCATAGTCCTACGACTGGT517EHSPTTG1734115.8995459GGGCTCACAGGATACCCAATG518GLTGYPM1735115.844460ACGATGGAATCCGGCCGCCAC519TMESGRH1736115.82461TCTGCGTCGAAAGTGGAATAC520SASKVEY1737115.719462GATAAGTCTAATTATAGTATT521DKSNYSI1738115.714463TTCAACGAAACTGCCGGGCGA522FNETAGR1739115.65464CAAAAATCGGAAACCTACACT523QKSETYT1740115.528465GCACTTACCCGTATGCCTAAC524ALTRMPN1741115.476466CGTAACGGCTCCGCCCAAAGC525RNGSAQS1742115.465467GCGAGGGATACGCCTGGGATT526ARDTPGI1743115.432468ATTGTTAATGCTGAGATTTAT527IVNAEIY1744115.31469CGACAAGGCGACTTAAAAGAA528RQGDLKE1745115.3059470CGAAACAACCCATCGCACGAC529RNNPSHD1746115.224471CTCGCCCACAACTACTTAAGC530LAHNYLS1747115.195472AACACCCACAACCTACAAATG531NTHNLQM1748115.171473CGAGGAGACCACAGCACACAG532RGDHSTQ1749115.12474CTCCACGGAGTCAGCAGTATA533LHGVSSI1750115.105475GGTATTAATCATGTGGCGTCT534GINHVAS1751115.102476ACTGATAAGCTTCAGGGTGTG535TDKLQGV1752115.062477GGAACCTCCATAGACTACGTA536GTSIDYV1753115.053478TCGAACACTGCCCCCCCCCCC537SNTAPPP1754115.034479ACTGCTAAGAGTTATGGGCCT538TAKSYGP1755115.006480GACCACCAACAAGCACTAGCT539DHQQALA1756114.98481ACACAAGTAGTCGCAAGAACA540TQVVART1757114.9299482AGTCCTCCTAGTACGTCGGGT541SPPSTSG1758114.816483CCTATGCGAACACCACCGTAC542PMRTPPY1759114.806484GCTGCTGGTAATACTACTCGT543AAGNTTR1760114.78485AGAGGCGACTAATCCACACCC544RGD*STP1761114.78486CTAGCGAAAACTGTCGCTATC545LAKTVAI1762114.722487TCTAAATCTGAAAACCTGCAA546SKSENLQ1763114.59488ACTCAGACGTCGTATGCTACG547TQTSYAT1764114.505489ACTGGGGATAGGACTTCGGTG548TGDRTSV1765114.4766490ATATCGCAAGGCTCGAGCCTC549ISQGSSL1766114.305491CTTGTTCAGATGGGGAGTGTG550LVQMGSV1767114.256492TTATCCGCAACATCTACGATG551LSATSTM1768114.245493CAAAACCACAACGAACTAAAA552QNHNELK1769114.217494CGTGGTGCGCCTGAGCATGCG553RGAPEHA1770114.09495TCTTCTTTCGGAAAAGACAAC554SSFGKDN1771113.982496AACGCTAACGCCGGTGGAAAC555NANAGGN1772113.958497GATCATCATCCTCAGAGTCGT556DHHPQSR1773113.83498ATGAGGCATGAGGCTCCTCTT557MRHEAPL1774113.819499AAGGGGGATGGTGCTTATGAG558KGDGAYE1775113.742500CCTATGAATGGTATTCTGTTG559PMNGILL1776113.722501AGTAGTGGGGGTATGAAGGCG560SSGGMKA1777113.69502GTGCTGGTTACTCAGAATCAT561VLVTQNH1778113.631503GAGATTAATAATCGGACTGGT562EINNRTG1779113.588504TTACCAACAGGCGTCCTGCCC563LPTGVLP1780113.561505GCCTACGGTATCAGAGAAGTG564AYGIREV1781113.547506TCGACAAACTCTATAGGCGCC565STNSIGA1782113.471507GTGCAGTTGACGCATAATGGG566VQLTHNG1783113.43508GTTCAGTTGGAGAATGCGAAT567VQLENAN1784113.43509GGAAAAGCCAACGACGGTTCT568GKANDGS1785113.427510ACCGGGGTTCGAGAAACCATA569TGVRETI1786113.41511GGCCTGAACCAGATCACATCG570GLNQITS1787113.4512ACGGAGAAGGCGAGTCCTCTG571TEKASPL1788113.381513TTTCTGGAGGGTGTTGCGCAG572FLEGVAQ1789113.333514ACGAATTATAATATTGGTCCG573TNYNIGP1790113.318515AGAGGAGACTTGACAACCACA574RGDLTTT1791113.29516ATGATGAATGTGAGTGGTCAT575MMNVSGH1792113.09517TCTCAGTCGATTAATGGGCTT576SQSINGL1793113.084518CTCACGACTTTAACTAACCAC577LTTLTNH1794113.033519AACTCTGTTCAATCCACCCCA578NSVQSTP1795113.021520TATAATACGGATCGGACTAAT579YNTDRTN1796113.001521GAGAAGCCTCAGCATAATAGT580EKPQHNS1797112.98522ACGATGGCTACAAACTTAAGT581TMATNLS1798112.937523GTGGGGACGCATTTGCATTCG582VGTHLHS1799112.918524GACGCCCACCACTCAAGCAGC583DAHHSSS1800112.88525CTTGTGGGGACTTTGGTGTAT584LVGTLVY1801112.853526TATGGTGTGCAGGCGAATAGT585YGVQANS1802112.806527GTTTTGTCTGATAAGGCGTAT586VLSDKAY1803112.787528CTTGAGGGTCAGAATAAGACG587LEGQNKT1804112.731529GAGGTTAGTAATAATAATTAT588EVSNNNY1805112.69530GCCCACCAACAAGCCCTAGCT589AHQQALA1806112.67531CTTCCGACCACACTCAACCAC590LPTTLNH1807112.667532TACATAGCAGGTGGTGAACAA591YIAGGEQ1808112.6513533AATTCTGGTACTCTTTATCAG592NSGTLYQ1809112.609534CGGGGTCTGCCTGATGTTAAT593RGLPDVN1810112.43535AACCAACAACTATCCCACTCA594NQQLSHS1811112.375536AATCCTAGTTATGATCATCGG595NPSYDHR1812112.363537ATAGACAGCGACACCTTCGTA596IDSDTFV1813112.355538ACCGCTTACCTTGCGGGATTA597TAYLAGL1814112.17539CATAGTAATGTTAGTCTTGAG598HSNVSLE1815112.162540GGTAATAATTTGAGTTTGTCT599GNNLSLS1816112.16541GTTATGGATACGCATGGGATG600VMDTHGM1817112.145542GCGTATAATATGTCGTCTGTT601AYNMSSV1818112.14543ACTAACGCCATCTCTCAAACG602TNAISQT1819112.063544GCAACACACGCCATGCGCCCA603ATHAMRP1820112.016545ATGTTAAACAACACAATGATG604MLNNTMM1821111.939546ATTAGTTCGGGGATTTTGTCG605ISSGILS1822111.907547CGCCAAGGCAGCTTGATGATA606RQGSLMI1823111.83548ACGACTGATAAGGGTATTAAT607TTDKGIN1824111.818549CACAACTTAATGACCCAAATA608HNLMTQI1825111.77550AACCAAAACACCTACGAACTG609NQNTYEL1826111.756551GCTAACACCGTCACAGAACGA610ANTVTER1827111.7323552TCTACGCTGCAGACTAATGGT611STLQTNG1828111.683553CCCAACGAATACAAAGCACCG612PNEYKAP1829111.646554ATGCAAACACGCTCGGACACA613MQTRSDT1830111.629555GGAACAGGGTACGCTGGATCA614GTGYAGS1831111.6183556ATGGGTATGCAGAATACGCAT615MGMQNTH1832111.599557TCTAGTAAGGAGCGTACATCG616SSKERTS1833111.57558CGAACGGACACCCCCTACACC617RTDTPYT1834111.562559ACTGCGCTGCGGGATAATAAG618TALRDNK1835111.51560AGGATGTCTGAGAGTTCGGAT619RMSESSD1836111.51561AACCAATCTATAAGCATGGAC620NQSISMD1837111.491562TCGCTTGGGCATAGTAATAAT621SLGHSNN1838111.432563CTTAATAGTGGTGGTGCGATG622LNSGGAM1839111.361564AACGAACAATTCGAAAAAGTC623NEQFEKV1840111.341565ATGATGGCGAATAATATGCAG624MMANNMQ1841111.28566AGTCGGCGCGAAGAACAACCA625SRREEQP1842111.2512567GCGACTATGACTTCGTCGACG626ATMTSST1843111.238568CGTGGTTCAGACGGAGGATTG627RGSDGGL1844111.172569AGTTTGACGCCTAATAATCTT628SLTPNNL1845111.152570GCTACTCTTTCTCCGCATGCT629ATLSPHA1846111.132571TATCTGCAGGAGAAGTTTCCT630YLQEKFP1847111.112572GGCACCGGGTACCCAAACCAA631GTGYPNQ1848111.111573AATTATCCTTCGGTTCAGGAG632NYPSVQE1849111.07574ACTGACGCATCGGGTAGATCA633TDASGRS1850111.017575CGTGTGATTACTGCGGGTGAT634RVITAGD1851111.009576GTGACTGTGAGTAATAGTCTG635VTVSNSL1852110.95577TTGTTGACGGCTCCGCATAGG636LLTAPHR1853110.908578TCAATCGCAAACCACATGATA637SIANHMI1854110.861579ATGCCTTCGAAAGGCGAAGTA638MPSKGEV1855110.816580AACATGACCAACGAACGGCTC639NMTNERL1856110.801581TCATTCTCTTCAGGCATAATG640SFSSGIM1857110.771582CGCGACCGTCAAGACTCGGTA641RDRQDSV1858110.754583CACGGTGACCGAACAGCTTTA642HGDRTAL1859110.748584GAAGTACGGGGCAGCGTGCCA643EVRGSVP1860110.747585CTGATTTCGACTGGTAATAAT644LISTGNN1861110.735586CCAACATCTGGGGACAAACCG645PTSGDKP1862110.735587AAAGCGGACCACAGTGGGGCA646KADHSGA1863110.73588CTAAACGACGTCTACCGTAAA647LNDVYRK1864110.724589AACAGTTTGCAAGCAAGTGCA648NSLQASA1865110.72590TATCATAATGAGATTATGACG649YHNEIMT1866110.708591AACAACACCCTAAACATCCTA650NNTLNIL1867110.69592TCTTATGGGCAGGGTCTGGAG651SYGQGLE1868110.684593ATGATAAAAACCAACATGTTG652MIKTNML1869110.668594ACCGAAGCGGGCCGCCCCCAA653TEAGRPQ1870110.663595AGGATTGATCAGACTAATGTG654RIDQTNV1871110.624596GAGGGGCATAATCGTGGTATT655EGHNRGI1872110.559597ATGGGGACTGAGTATCGTATG656MGTEYRM1873110.524598TCGGGTATGAATAGTAATAAG657SGMNSNK1874110.499599TTGACTAATGATAATAAGTTG658LTNDNKL1875110.479600TTACACAACTACCAAGACCGT659LHNYQDR1876110.438601AAGTCTAATTTGGAGGGTAAG660KSNLEGK1877110.438602CTTACTGGTCAGAATGCGATT661LTGQNAI1878110.416603CATACTGTGGGGGCTATGCAT662HTVGAMH1879110.41604CTCCAACTGGCTACATCCCAC663LQLATSH1880110.384605AGTCTGAATGGGGTGTTGGTT664SLNGVLV1881110.359606AGTCACAACCAAGTAAACGTA665SHNQVNV1882110.349607AGTTTGAGTACTGATGTGTTT666SLSTDVF1883110.261608ATGGTAGGTCGTGCCGAAATC667MVGRAEI1884110.224609TTGTCTAGTATGAGTACGGAT668LSSMSTD1885110.204610TCCTACAGTACTTCAACACCG669SYSTSTP1886110.189611TCCGAATTAATGGTCAGACCC670SELMVRP1887110.0813612TGGAACGGAAACGCCACACAA671WNGNATQ1888110.039613ATGGATACTGAGCTTTATAGG672MDTELYR1889109.985614AGGACGAGTCCTGATACGAAT673RTSPDTN1890109.977615TTCTCAACGCAAGACATAAGC674FSTQDIS1891109.948616ACGACTGTGCTGGGGAATAAT675TTVLGNN1892109.94617CAGCGTGATGCTGCGTATGCT676QRDAAYA1893109.927618CACCAAACCGTGGTCCCTACT677HQTVVPT1894109.8948619TCTAATCCGGGTAATCATAAT678SNPGNHN1895109.853620TGGGAGACTATGGCTAAGCCT679WETMAKP1896109.818621GGTCTTTATCAGAATCCTACG680GLYQNPT1897109.73622CTTAATCTTACTAATCATAAT681LNLTNHN1898109.727623ATGAGTCTCGCCTCCACCCAA682MSLASTQ1899109.672624ACGTCCCAAACCGTCCGAGTA683TSQTVRV1900109.654625GGAGCAACGGTCAACACGCGA684GATVNTR1901109.64626AAAGGGGGAAACCTCACCGCA685KGGNLTA1902109.632627GCGTGGTCTCAAGTCCTGACG686AWSQVLT1903109.587628GTAGAACACGTAGCCCACCAA687VEHVAHQ1904109.552629CTAATGTCGTCCTACTCATCA688LMSSYSS1905109.546630TCTCTGGGTGGGAATCCGCCT689SLGGNPP1906109.511631AAGAATGAGAATACGAATTAT690KNENTNY1907109.5055632ATATTGGACAACCACCGTTTC691ILDNHRF1908109.489633AATTCGTCGCATGTTAATTCT692NSSHVNS1909109.473634CAGGTGCAGCATGAGAGGGTG693QVQHERV1910109.47635TTGGGAGGAACCCTGGGAATA694LGGTLGI1911109.46636ACTCAAGAACGACCACTAATC695TQERPLI1912109.455637CGTAAGACTGAGGATAGGATG696RKTEDRM1913109.429638ACCGAACTCACAGCGCGGAAC697TELTARN1914109.398639CGCGGCGACAACACTTACTCC698RGDNTYS1915109.387640CAGTCTAATACTAATAATAGT699QSNTNNS1916109.372641GCTTCTTATAGTATTTCTGAT700ASYSISD1917109.309642AGCGAACACCACGCCGGAATA701SEHHAGI1918109.281643CGTGGTGCGCCAGAGCATGCG702RGAPEHA1919109.237644AATTTTAGTAGTGGTGATGTT703NFSSGDV1920109.229645AGTGGCATCAACGCCACCGAC704SGINATD1921109.22646CGGGCTGATGTTTCTTGGTCT705RADVSWS1922109.213647TGTATGGATGTTGGTAAGGCG706CMDVGKA1923109.203648GGGGTCGGAGCCACTTCGGTA707GVGATSV1924109.193649AAAAACAACAACTCAGACAGT708KNNNSDS1925109.177650AATGTTGCGAGTATTGATAGG709NVASIDR1926109.174651AATAGTGTGAATGGTCTTCTG710NSVNGLL1927109.154652ACACTAGACCGAAACCAAACC711TLDRNQT1928109.132653GACCAAAACTTCGAACGTAGA712DQNFERR1929109.108654GTCGGTGACAGGAACTTGGTC713VGDRNLV1930109.062655TTAGAAGTAAACCTGCAAACG714LEVNLQT1931109.057656ACTAATGGGGGGTCGCTTAAT715TNGGSLN1932109.049657TTCACGCGCACACCAGTAACC716FTRTPVT1933109.033658ACACCGGCGGAAAGCAAAGTT717TPAESKV1934108.991659TTTCCTTCGCATAATGGGGCG718FPSHNGA1935108.959660GCCAGGAACGTAATGCTGGGG719ARNVMLG1936108.958661ACGATTCAGGATCATATTAAG720TIQDHIK1937108.942662ATTAATTCGTATTTGCATGAG721INSYLHE1938108.918663GCGCATGATGTTACTGTGAAT722AHDVTVN1939108.918664ACTGTGGGGGTTCAGCAGACG723TVGVQQT1940108.8891665ACAGGTAGTTCAGACAGATTA724TGSSDRL1941108.887666AATCATGATACTGCTCATGCT725NHDTAHA1942108.884667GCCGAATCCCAACTAGCTAGC726AESQLAS1943108.8752668GGTAATGCGTATAATACGACT727GNAYNTT1944108.818669AATCATCAGGCTGGTACTACT728NHQAGTT1945108.807670ACGGTAGGAGAAAACCACCGA729TVGENHR1946108.779671CTAACTACTAAAATACCCCTC730LTTKIPL1947108.773672ACTAATTATCCTGAGGCGAAT731TNYPEAN1948108.748673AATACTGCTCCGCCGAATCAT732NTAPPNH1949108.733674GTGCTGAGTACGGGGCTGCGG733VLSTGLR1950108.677675CTCACGTCCCACTCTGCGGGC734LTSHSAG1951108.648676ATGAATAAGCATGGTGTGCTT735MNKHGVL1952108.5736677GACCTGACCAGAGCTGCAATA736DLTRAAI1953108.552678TATATTGTGGATCATGCGAAT737YIVDHAN1954108.526679AGTGGGCCTGAGAATACGTTG738SGPENTL1955108.526680CGTTATGGTGATACGGGTATG739RYGDTGM1956108.512681GATGGTAAGAATAGTTATGCG740DGKNSYA1957108.451682GAGGCGCATAATCGTGTTATT741EAHNRVI1958108.451683AGTTTGCAGGCTGGTAGGATG742SLQAGRM1959108.3681684GATGCGAAGGCTCTTACGACT743DAKALTT1960108.368685ACCGACACCCGAAAAAACGAC744TDTRKND1961108.357686GACTCTTCACACTACTCGACA745DSSHYST1962108.219687ACAATGCACCTTCCCAACCTG746TMHLPNL1963108.214688CGAGACGGCTCTACTAAAGTT747RDGSTKV1964108.207689TCAGGGTACCAAATGACAGAA748SGYQMTE1965108.16690TGCGACTTGTCACAATCATGC749CDLSQSC1966108.133691AGAAACGCGTCAAACGGCGTA750RNASNGV1967108.044692CAGTCGCAGAATGTGACTCAG751QSQNVTQ1968108.033693GATTCTGCTCCGAGTACTATT752DSAPSTI1969108.003694AGGTCCGTACCATCACCACAC753RSVPSPH1970108.001695ATGACGTCTGCGTCTCGTGGT754MTSASRG1971107.974696GCTCTTGCTAGTCGTCCTATG755ALASRPM1972107.907697CTAAACCTCTCCAACGACTGG756LNLSNDW1973107.899698GTTTCTACGGCGCAGAGGCAG757VSTAQRQ1974107.896699CACGCCGACGTTGGCATGAGC758HADVGMS1975107.888700GCGGGGGGTTTGCTGTCGCGG759AGGLLSR1976107.878701CATCTTAGTCAGGCTAATCAT760HLSQANH1977107.848702GTGCATAATCCTACTACTACG761VHNPTTT1978107.8152703TCTCAGCGGAATCCGGATGAT762SQRNPDD1979107.784704AGGGAGACTAATAATTTTGCG763RETNNFA1980107.771705AATGCGGGGGCTCTTATGGGT764NAGALMG1981107.764706TTGCCGAAGACTGTGAATATG765LPKTVNM1982107.738707GCAAGTGACCTACAAATGACG766ASDLQMT1983107.723708CAAGCCCTGGCCACCACAAAC767QALATTN1984107.716709CATGAGTCGTCTGGTTATCAT768HESSGYH1985107.696710GGGGTGAATGATCGTGCTAGG769GVNDRAR1986107.69711CCTCGGGATGCTCTTCGTACT770PRDALRT1987107.673712AACGACTCCTCGTCAATGTCC771NDSSSMS1988107.641713GAATACAACACGCGCCACGAC772EYNTRHD1989107.611714GCGTCTCCGGCGCATACGTCT773ASPAHTS1990107.598715CAAAACAGCAACACTCCCTCA774QNSNTPS1991107.546716TTGGCAAAACTAGGGAACTAC775LAKLGNY1992107.541717GCTAGTGATAGGCAGTCTGGT776ASDRQSG1993107.527718TATCAGAATGGTGTGCTTCCT777YQNGVLP1994107.5199719AATAAGTTTGGTTATAATCCT778NKFGYNP1995107.513720AAAAAAACCAACGGAATCCCC779KKTNGIP1996107.5721GTTAACGACAACCGAGGAAAC780VNDNRGN1997107.4937722ATGCACACCATAACGGGATCC781MHTITGS1998107.491723ATTGATGGTGTTCAGAAGCTT782IDGVQKL1999107.489724GCGCAGGTTAATAATCATGAT783AQVNNHD2000107.489725GTTTCTTCGCCTAATGGTACG784VSSPNGT2001107.487726GATTCTGCTCCGAGGGCTATT785DSAPRAI2002107.455727TCTGCGAGTGATAGTCAGCAT786SASDSQH2003107.455728TCGGCTCATCAGACGCCGACG787SAHQTPT2004107.427729GCGACGCTGAATAATAGTTAT788ATLNNSY2005107.411730GAAGACAGTATGAGATTCTCT789EDSMRFS2006107.407731GAACGAAACGGACTAATAGAA790ERNGLIE2007107.405732TTAGTACTTGACTCACGGAAC791LVLDSRN2008107.382733ACCGTCGAACAAATAAACTCG792TVEQINS2009107.349734GGGACAGGTACCGTTGGATGG793GTGTVGW2010107.203735AATCAGCAGCGTATTGATAAT794NQQRIDN2011107.185736ATCCAAAACGGGGTCCTGCCA795IQNGVLP2012107.184737GGAGACATCTCAAGCAGAAAC796GDISSRN2013107.1386738GTCACTGGCACTACCCCGGGA797VTGTTPG2014107.137739ACAAGGGAATCAATGTCCATC798TRESMSI2015107.071740CACACTTACTCACAAGCAGAC799HTYSQAD2016107.012741TCCAACATGGGCGTAGCCTCT800SNMGVAS2017106.985742CACGACTTGAACCACGGAAAA801HDLNHGK2018106.942743CTGTACGGGGGAGCACACCAA802LYGGAHQ2019106.904744AACGTGTACGGAGACGGAATA803NVYGDGI2020106.87745TCTACTATTAATATGCGTGCG804STINMRA2021106.868746AAGATGGGGAGTATTGAGGTT805KMGSIEV2022106.864747TCCGAAACGCGCGCTGGATAC806SETRAGY2023106.85748AATGTGGGTAATACTCTTGGG807NVGNTLG2024106.842749ATTGGTGGGACTGATACGCGG808IGGTDTR2025106.786750GCCGACAAAGGATTCGGCCAC809ADKGFGH2026106.73751TGGCAGGATCATAATAAGGTG810WQDHNKV2027106.719752AACTACGGTTCCGGACGAATC811NYGSGRI2028106.701753ACTCATAAGCAGGTGGATCTT812THKQVDL2029106.695754CGGCAGAATGATAAGGGTAAT813RQNDKGN2030106.658755GGTAGGAATGAGAGTCCGGAG814GRNESPE2031106.658756GTTTTTACTGGGCAGACGGAG815VFTGQTE2032106.632757TATGTTGATCGTAAGGATAAT816YVDRKDN2033106.631758AATAATACTTTGAATATTTTG817NNTLNIL2034106.63759TTGAGCTACAGCATCCAACAC818LSYSIQH2035106.621760GCTACCAACAGATCGCCCCTA819ATNRSPL2036106.5898761GTTCACACCGCAGACACAATA820VHTADTI2037106.564762GGGCATTTGGTTAATATGTCT821GHLVNMS2038106.56763TTAGACTACACCCCTCAAAAC822LDYTPQN2039106.519764TCCGCCTCTTACTCCAGGATG823SASYSRM2040106.501765TCCGGAGCGGCACAAAACCCA824SGAAQNP2041106.499766AGAAACACACTTGCTGACCTT825RNTLADL2042106.496767GGTTCTACGGTGTCGGCGCAG826GSTVSAQ2043106.491768TCTAAGGATAGTACTATGTAT827SKDSTMY2044106.48769GTGGTGGTTCACACTATCCCA828VVVHTIP2045106.45770CCACGTACTGTCTCATTGGAC829PRTVSLD2046106.4434771ATGATGAAGAGTGAGGAGAAT830MMKSEEN2047106.425772ACCACCGACCGGCCAAACGGA831TTDRPNG2048106.406773CATAGTCCTCCTACGACTATG832HSPPTTM2049106.376774GGCCAATGGACAACAGGGACA833GQWTTGT2050106.357775GACGGTATGAACGGAGTGGGT834DGMNGVG2051106.317776CTTCATACTGTTGCGAATGAG835LHTVANE2052106.312777TATACGTCGCAGACGTCTACG836YTSQTST2053106.2842778AACTTCTCCGAAATGTCCACA837NFSEMST2054106.27779ATTAATATTCGTAGTGATTTG838INIRSDL2055106.266780CCCTCCAACAGTGAAAGATTC839PSNSERF2056106.249781TATACGAATTATGGGGATCTT840YTNYGDL2057106.241782GATAAGAGTACGGCGCAGGCG841DKSTAQA2058106.238783CACACCGACATGGTATCCTCT842HTDMVSS2059106.222784AACAAAAGTCTGTCAATGGAC843NKSLSMD2060106.196785GGGCACTACGCTACAAACACA844GHYATNT2061106.158786GTCATCGTATCTACAAAATCA845VIVSTKS2062106.124787ACTCATAGTCTTATGAATGAT846THSLMND2063106.116788AACTACCACGGAGACAACGTT847NYHGDNV2064106.106789CGTGATGATCAGCAGCTTGAT848RDDQQLD2065106.064790GATGATAAGACTGGTCGGTAT849DDKTGRY2066106.055791GGGTCGAGCCAACACCACGAA850GSSQHHE2067106.042792CGTGTTACAGGTGTCTCAACA851RVTGVST2068106.017793AGTACTGCGTCGGGGCATACT852STASGHT2069106.007794ACTAACAACCTCTCATACGAA853TNNLSYE2070105.998795CAGCATAATAGTGCGTCGGCG854QHNSASA2071105.987796CCGGCTAAGGGTTTTGGTCAT855PAKGFGH2072105.9781797TGGTACGAAACAATCAGCCCG856WYETISP2073105.959798ACGGATGCTACGGGGAGGCAT857TDATGRH2074105.942799ATTCAGGCGAAGAATTCTGAG858IQAKNSE2075105.939800AGTACTGAGACTAGGGGTGGG859STETRGG2076105.926801TTCTCAACAAACTCTGTAATC860FSTNSVI2077105.918802TCTAACCTTCGAAACACAATA861SNLRNTI2078105.854803GGGATGATCGGGCACAACGCA862GMIGHNA2079105.832804TCTGGCCAAGGATTCTCGGCA863SGQGFSA2080105.831805ACCCACAACTCTACAGGCCTT864THNSTGL2081105.802806AGGATTGATAGTGCTATGGTG865RIDSAMV2082105.8807GTCGCTATGGGAGGCGGTCCC866VAMGGGP2083105.795808GGCTCTCACAACGGCCCAGCC867GSHNGPA2084105.763809CACTCCGCAGCGGGTGACGGT868HSAAGDG2085105.73810GCACAAGGCATAACCCACGCT869AQGITHA2086105.711811TCTGCGCTTTTGCGGATGGAT870SALLRMD2087105.707812TGGCAAATGGGGGCCGGGAGC871WQMGAGS2088105.698813ATAGACTCGCACGCCAGCATA872IDSHASI2089105.695814AGCCTAGACCACGCCCCTCTA873SLDHAPL2090105.661815GAAAACAACATGCAACACGGC874ENNMQHG2091105.651816AAGGGTGCGCAGGGTGTTCAG875KGAQGVQ2092105.646817GTCGCTGTATCGAACACTCCA876VAVSNTP2093105.643818GTTGAGTCTTCTTATTCTCGG877VESSYSR2094105.633819CATAATACGGAGTCTAAGACT878HNTESKT2095105.625820AATGAGAGTACGAAGGAGAGT879NESTKES2096105.599821GATGTTTATCTTAAGAGTCCG880DVYLKSP2097105.586822CAGTCGGGGGCTAGGACTCTG881QSGARTL2098105.5854823TCGAACAGTCAAGTACACAAC882SNSQVHN2099105.573824GTAGTCTCATCGGGCGGCTGG883VVSSGGW2100105.551825CCATCAAGTTTCAACAGCGCC884PSSFNSA2101105.542826AAGCAGACTGATAGTAGGGGT885KQTDSRG2102105.5827AACACAACGCCACCTAACCAC886NTTPPNH2103105.483828CAAAACGGAACCTCGTCTATA887QNGTSSI2104105.483829CTCATGAAAGACATGGAATCC888LMKDMES2105105.458830ACTCAGACTGGTCATGTTTCT889TQTGHVS2106105.4558831GAAATACACACGACCACAGGC890EIHTTTG2107105.449832ATACAAACTACTACAAAATGC891IQTTTKC2108105.442833CCCGCTGAAGGAAACAACCGT892PAEGNNR2109105.442834TACATCGCCGGAGGGGAACAA893YIAGGEQ2110105.415835GAAGTACGCGACCAAAAAACA894EVRDQKT2111105.375836TACGCCGTCGCGATAGGCACA895YAVAIGT2112105.366837TCCGCTAACGAACACAACCAC896SANEHNH2113105.337838GGGATGAGGGATACGCCGCCG897GMRDTPP2114105.322839GCTCAGCAGATTGTTAATGGG898AQQIVNG2115105.321840TCAAGTTCCCAAACGGTTTTG899SSSQTVL2116105.321841GTTATTCAGTCTGATAATACG900VIQSDNT2117105.32842GTTCCGGCGCATTCTCGGGGT901VPAHSRG2118105.305843TCGAATACGGGGTCGTTGGGT902SNTGSLG2119105.2779844TGGGCCAAAGACGTCAACGTC903WAKDVNV2120105.273845AATGTGTTGGGTGCTTCGAGT904NVLGASS2121105.187846ACTCCGGAGGCTAGTGCGCGT905TPEASAR2122105.173847AATTATAATGGGGTTAATGTG906NYNGVNV2123105.152848AACACAACCGGTAGCTCGGGC907NTTGSSG2124105.145849TCCAGCGGCCAACCGCTCGTC908SSGQPLV2125105.136850CAGGCGGGGGGTGTGGCGAGT909QAGGVAS2126105.133851CCGCTTCAATCCCAATCGGGA910PLQSQSG2127105.133852CAACGTACCTCGGAAGCGCCA911QRTSEAP2128105.128853TTGGCTAAGACGGTTGCGATT912LAKTVAI2129105.1155854ACCCACACCCTTGGGGGAACA913THTLGGT2130105.08855CACGACTACAGTATGAACGCG914HDYSMNA2131105.079856GGGAAACCTGCGGAAGCGCCG915GKPAEAP2132105.055857AGAAACGAAAACGTAAACGCT916RNENVNA2133105.051858AGTTCTCGGGAGGCGAAGTTT917SSREAKF2134105.0379859TCTTCTTCTGATAGTCCGCGT918SSSDSPR2135105.035860ATGAATACGACTTATAATGAG919MNTTYNE2136105.031861GTAAGGAGTGGAATAAAACCA920VRSGIKP2137105.008862CAGGAGAATCCTATGAAGATG921QENPMKM2138104.926863ACTGAGCCGCTTCCGATGTCT922TEPLPMS2139104.869864CGCCACGGGGACACACCGATG923RHGDTPM2140104.844865GCGGTGAATACGTATAATAGT924AVNTYNS2141104.82866GCGTCGACTGAGTCTCATGTG925ASTESHV2142104.816867ACAAACCTAAGTCAATCGGCC926TNLSQSA2143104.791868GAGCTGTCTACTCCTATGGTT927ELSTPMV2144104.783869TATGCGCATCCTGTGACTCAT928YAHPVTH2145104.76870CGGGGGTCTACTGGTACGCAG929RGSTGTQ2146104.749871TGTGTTGGTTCGTGTGGTGTG930CVGSCGV2147104.738872TCGGTTGCTAAGGATCAGACG931SVAKDQT2148104.736873ACGAATCTTTCTCCTAAGACG932TNLSPKT2149104.6855874CTAGGTTTCACACCCCAACCG933LGFTPQP2150104.677875AATATTAGTAGTATTAATCAG934NISSINQ2151104.657876GTTTACGACAACGTTTCTTCT935VYDNVSS2152104.657877AGTGGAAAACAAGACAAATAC936SGKQDKY2153104.654878AGACTTACAGAACTGGTCATA937RLTELVI2154104.651879CATAAGAGTGAGAGTCATAAT938HKSESHN2155104.626880GAGGCGACTCATGGTTCTTAT939EATHGSY2156104.613881AACCTACTTGTCGACCAACGT940NLLVDQR2157104.579882AATATTAATGATACTAAGAAT941NINDTKN2158104.522883CTTGCGGTTACGAATGTGCGG942LAVTNVR2159104.498884CCGTCGACACTCGCTGAAACA943PSTLAET2160104.449885CCGAAGCCTGGGACGGGGGAG944PKPGTGE2161104.427886GTGCTGTTGCAGAATTCTCAT945VLLQNSH2162104.416887TACGGTAACGCGAACACCGTA946YGNANTV2163104.386888ACATCTGGAGTTCTGACACGC947TSGVLTR2164104.375889AAAATAACGGAAACCAACCTC948KITETNL2165104.359890GTTCGCAGAGACGAAACACCT949VRRDETP2166104.359891TCTAAAATGTCAAACCCAGTG950SKMSNPV2167104.352892TGGGAATCCCTCTCCAACGCA951WESLSNA2168104.349893GCCAACGGAGGAGGATACCCC952ANGGGYP2169104.34894ATGTTGGCTTCTCGGGTGCCT953MLASRVP2170104.336895TGCGGCCTGAACTGCGGTAAA954CGLNCGK2171104.331896ACTATTACTAGTCCGTCGGTG955TITSPSV2172104.3055897TGGTCGAATGCTCAGAGTCCG956WSNAQSP2173104.288898ACAGAAAGCCCCAAACTACTA957TESPKLL2174104.283899CATTTGGTTACTAGTGGTATT958HLVTSGI2175104.273900CCTCCTAAGTCGGATTCGAAT959PPKSDSN2176104.265901ATTGCGGTGCATGTGCTGAGT960IAVHVLS2177104.254902ACTGGTACTGCGACTTTGCCT961TGTATLP2178104.254903AATACTACTCCGCCTAATCAT962NTTPPNH2179104.232904TGCACCGCCACAAAATGCTCA963CTATKCS2180104.23905CACAGTGACATGGTCAGCGGC964HSDMVSG2181104.208906CCAAACGCACACCACCTGCCC965PNAHHLP2182104.2907TCTAATAATATGAATCAGGCG966SNNMNQA2183104.187908AGTGATAATAATAGGGCTAAT967SDNNRAN2184104.1865909TTGCAGACGCCTGGGACGACG968LQTPGTT2185104.169910GTGCGCGGCGTTCAAGACGCC969VRGVQDA2186104.167911TCTCTAGACTCGCGCTCCTCG970SLDSRSS2187104.14912GTTTGTGTTACTACTTGTGCT971VCVTTCA2188104.137913CCGAATACTAATCATCTTGTG972PNTNHLV2189104.121914CTCATGTCAGGGAAAGAAAAC973LMSGKEN2190104.109915ACTTCTGCTAGTGAGAATTGG974TSASENW2191104.108916TTTTTGCCGCAGCTGGGGCAG975FLPQLGQ2192104.094917CCTTTTAATCCTGGGAATGTG976PFNPGNV2193104.0922918GGGACACCTGGTCAAAGTATA977GTPGQSI2194104.092919TATAATAATGGTGGGCATGTT978YNNGGHV2195104.085920CTCGGAAACCACTACACACCC979LGNHYTP2196104.064921CAAGTCAACCAACCGAGAATA980QVNQPRI2197104.061922TTAGGAAACAACCGGCCACTA981LGNNRPL2198104.06923CCTCCGGAAAGTGCCAGGGGC982PPESARG2199104.023924AAATCTGTAGGCGACGGGAGA983KSVGDGR2200104.0009925TCACTTCGGACGGACGAATTC984SLRTDEF2201103.997926AGTACTACTAATGTTGCGTAT985STTNVAY2202103.987927AGGATGTCGGATCCTAGTGAT986RMSDPSD2203103.981928AGTCTGTCTATTACTTCGGCG987SLSITSA2204103.963929GAAAGTGCCACATCTCTAAAA988ESATSLK2205103.954930TACACTGACGGAAGAAACACC989YTDGRNT2206103.949931TCCATATCCAACCTGCGTACC990SISNLRT2207103.935932CAAAACGACAAATCTGACAAC991QNDKSDN2208103.9165933GGTGGAACAGGTCTTTCCAAA992GGTGLSK2209103.916934AGTCAGGCTCAGATTCGTGTT993SQAQIRV2210103.915935GGTTTGATGGCGCATGTGACT994GLMAHVT2211103.877936CTGGTTGTTTCGAATAGTCTG995LVVSNSL2212103.865937CATGATTCTGTGAATACGGCG996HDSVNTA2213103.8588938ACTCTTGCGAAGGATGGGAAT997TLAKDGN2214103.842939TCCGACGGATCGAAACTACTA998SDGSKLL2215103.829940ATAGACAAAACGTTCTCGGTC999IDKTFSV2216103.812941CGGCTGGTTAACATCGACCAC1000RLVNIDH2217103.8026942AAAAACTACGACAGTGACTCA1001KNYDSDS2218103.794943AGTACGCAGAGTACTAATCCG1002STQSTNP2219103.7868944CAAATATCACTACAACTCGGC1003QISLQLG2220103.77945TCCGAACCCCTTAGAGTTGGA1004SEPLRVG2221103.749946AGTCGTCTGCAGACTCAGCAG1005SRLQTQQ2222103.7406947GAAGGTTCACAAGGAAACCAC1006EGSQGNH2223103.739948CGTTCTGACCTTACTGAAAGT1007RSDLTES2224103.736949CATACTGGTGTTCAGACTAAT1008HTGVQTN2225103.724950GAGTTGGATCATCTTTCGCAT1009ELDHLSH2226103.714951GTTACTGGTGTTGATTATGCG1010VTGVDYA2227103.713952GGCGGCGCACACACTCGTGTA1011GGAHTRV2228103.676953GCCTACGGTATACACGAAGTG1012AYGIHEV2229103.653954GCGATGCTGCGTATGGAGCAG1013AMLRMEQ2230103.652955AGGCAGGCGAATCAGACGTAT1014RQANQTY2231103.652956TTTTCTGGTCAGGCGTTGGCT1015FSGQALA2232103.646957GATAATGTGAATTCTCAGCCT1016DNVNSQP2233103.646958GGGTTGCATGGGACGAGTAAT1017GLHGTSN2234103.633959GAGAGGGAGCCTCCTAAGAAT1018EREPPKN2235103.621960GTGGTGACGCTTGGGATGCTG1019VVTLGML2236103.619961CATAATAATAATTTGCTGAAT1020HNNNLLN2237103.612962TTGATTAATATGAGTCAGAAT1021LINMSQN2238103.6963AATACTAATGCGTCGTATTCT1022NTNASYS2239103.599964AGGCTTAATGCGGGTGAGCAT1023RLNAGEH2240103.594965GCTGTTATTCTGAATCCTGTT1024AVILNPV2241103.576966CCGAGTACTCATGGGTATGTT1025PSTHGYV2242103.571967CTTAGGGCGTCTGTGTCGGAG1026LRASVSE2243103.564968ATGATGACCTCTATGACGTTA1027MMTSMTL2244103.561969TCGGCACACAACATAGTATAC1028SAHNIVY2245103.556970CACGACAGCACAACCCGCCCA1029HDSTTRP2246103.545971ATCAAAGACTCGTACCTTACT1030IKDSYLT2247103.542972TATACGCCTGGGCTTACTGAG1031YTPGLTE2248103.541973AAGATGGGTGGTTCTCAGAGT1032KMGGSQS2249103.477974TCACGTCAAACAGCGCTAACA1033SRQTALT2250103.4599975GTAGAAACCAGCAGATTGTAC1034VETSRLY2251103.45976AAATCCAACAACGGGGAATAC1035KSNNGEY2252103.424977TCGGGTGTTCATAGTGCGCGT1036SGVHSAR2253103.3881978CCTAACAACGAAAAAAACCCG1037PNNEKNP2254103.326979ACTATTGGTGAGGGGTATCAT1038TIGEGYH2255103.325980CTGCAGACTTCTGTTGCTACT1039LQTSVAT2256103.316981CTATTGGGAAACGCACCCACA1040LLGNAPT2257103.308982ATTTCGGGGTCTCATTTGAAT1041ISGSHLN2258103.297983AAGTCTCTTAGTAGTGATGAT1042KSLSSDD2259103.285984ACGAGGACTCAGGGGACGTCT1043TRTQGTS2260103.2635985GTTAGTAGGTCTGGGAGTACT1044VSRSGST2261103.257986AGCGCCGACACCCGGTCCCCC1045SADTRSP2262103.242987CGTGATACTGCTAATGGGCCG1046RDTANGP2263103.2389988ATGATGTCTAACAGCCTCGCG1047MMSNSLA2264103.232989ACTGGGAGGATTGAGCTTAGG1048TGRIELR2265103.214990GCTAATAATGCGGCTGCGTCG1049ANNAAAS2266103.209991CAGTTGAATATTAATGATAAG1050QLNINDK2267103.208992ATGGACGGGGCTCACACGTCA1051MDGAHTS2268103.202993ACTAGTGCGACTGATTCGATG1052TSATDSM2269103.197994GCCGCCAGCTTGTCGCAAAGC1053AASLSQS2270103.152995TCTCAGGCGGGTCTGCTTGTG1054SQAGLLV2271103.116996ACGACTTATTCGGATCTGAGT1055TTYSDLS2272103.104997TTCTCCTCCGGAACAACCATA1056FSSGTTI2273103.102998GTCTTCACAGAAATAGAATCG1057VFTEIES2274103.101999GCAGACCCCGCTAAAGGCAAA1058ADPAKGK2275103.0831000AAAGAATCTGAATACAGAGTT1059KESEYRV2276103.071001GGGATGGTGTCTCTTAATAGG1060GMVSLNR2277103.061002ACCGTTATCGAACGCAAAGAC1061TVIERKD2278103.05751003AGGATTGATACGTTGTTGGTG1062RIDTLLV2279103.0551004GGATCCACAGGCCTACCCCCG1063GSTGLPP2280103.0471005ATGGAGTTGACTTCTACTAGT1064MELTSTS2281103.0261006CAACCAGGAGCCCCCCAAACC1065QPGAPQT2282103.0141007AATTCGATGGGTAATGGGGGT1066NSMGNGG2283103.0091008GGTAGTACTAAGTCTGGGCAG1067GSTKSGQ2284103.00491009ACTTTTTTGCCTCAGCTTGGG1068TFLPQLG2285102.9941010ATGGGAATAAACGTACTGAGC1069MGINVLS2286102.9861011GTGAATCTTGGTATTTCGGGG1070VNLGISG2287102.9851012AGTGAGAATCGGGCTGGTAAT1071SENRAGN2288102.9451013CACTCCAACGCGACTACGATA1072HSNATTI2289102.9161014CCGGGGTCGTCCGCTTCCATC1073PGSSASI2290102.9141015ATTACGTCGTTGAATGGGATG1074ITSLNGM2291102.9091016TATCTGGAGGGTGCTCATCGT1075YLEGAHR2292102.8961017AGGCAGGTTGAGCAGTCTGAT1076RQVEQSD2293102.8891018AGCTCTCAAAGTTCCGGGTCG1077SSQSSGS2294102.88361019CAGCTTACTGTTGGGAAGCCG1078QLTVGKP2295102.87621020GTTGTGCATTCGAGTATTACT1079VVHSSIT2296102.82571021CTAGAACAACTACGGGTCCCA1080LEQLRVP2297102.8151022CAGCATTCTCCGAAGCCGGTT1081QHSPKPV2298102.811023GCGGGCAGTTCGCCATCACGC1082AGSSPSR2299102.80351024GGAGTAACAATCGGTAGCAGG1083GVTIGSR2300102.77521025TACATCGCGGGAGGCGACCAA1084YIAGGDQ2301102.751026ATTAGTAGTGAGAGGTTTTCT1085ISSERFS2302102.7291027AGGAGTGAGGGTAATCATGCT1086RSEGNHA2303102.7191028GAGAAGGGGAATAGTGGGGTT1087EKGNSGV2304102.711029TACATAGTTGACCACGCTAAC1088YIVDHAN2305102.711030CGTCGGTTGAGTACGGATCTT1089RRLSTDL2306102.7021031GCGAATAGTAGGCTTGGGGCG1090ANSRLGA2307102.69791032GGTACTGCTGAGAATACGAGT1091GTAENTS2308102.6961033GTGAGGGATGTTGCTAAGGAG1092VRDVAKE2309102.6911034GGAGGCCTTACCAACGGTCTA1093GGLTNGL2310102.671035CCTTCGATTCCGTCGTTTTCG1094PSIPSFS2311102.6571036AACGCTCTCCTCAACGCACCT1095NALLNAP2312102.6281037GACGACATGGTCAAAAACTCA1096DDMVKNS2313102.6231038ACTGCGAATACGCATGCTCTG1097TANTHAL2314102.6131039GTATACGCCACCGCACTCGCA1098VYATALA2315102.6111040GGTATATACCCGGCATCCACC1099GIYPAST2316102.611041GGTTTTGATGGTAAGCAGCTT1100GFDGKQL2317102.6061042CACTCTATGTCCGCAAACACC1101HSMSANT2318102.6051043TGGAGCATCAAAAACCAAACA1102WSIKNQT2319102.5861044ACCCTCCACACCAAAGACCTA1103TLHTKDL2320102.571045TCTTATGGTAATACTCATGAT1104SYGNTHD2321102.5661046CAGTCGGGGTCTCTGGTGCCG1105QSGSLVP2322102.5521047AATACTTTGCAGAATAGTCAT1106NTLQNSH2323102.55061048ACGGCTGAGTCTAGTCATCCG1107TAESSHP2324102.5481049GCCTCTACAGTCTCACTCTAC1108ASTVSLY2325102.5471050CTGACTGCTGTTGCGATTAGT1109LTAVAIS2326102.5421051GTCTCGGGACAAAGTGCGTAC1110VSGQSAY2327102.5411052GGTGAAACTAACTTCCCAACT1111GETNFPT2328102.5321053AATGATAATAGGTCGATGAAT1112NDNRSMN2329102.5261054CGATCAGGCGACCCTAAAAAC1113RSGDPKN2330102.5191055TGGGAGAGTGATAAGTTTCGT1114WESDKFR2331102.5141056CAGGTTAATCATAATACTAGT1115QVNHNTS2332102.5141057GGGTGGTCGAACAACGAACTA1116GWSNNEL2333102.5071058CGGGCTGTGCTTGCGACTAAT1117RAVLATN2334102.491059CATATGGGTTTGAATGAGCTT1118HMGLNEL2335102.4841060GGAGAAAGCTCCTCAATAAGC1119GESSSIS2336102.4771061ATACACAAATCTAGCGTCGAA1120IHKSSVE2337102.4731062ATGTCCGGATCCATGATATCA1121MSGSMIS2338102.4631063TTGAGTCTGGCTGGGAATAGG1122LSLAGNR2339102.4481064TCTGCAACAACGAACCACGGA1123SATTNHG2340102.4411065TCTACGGAGTCTAATGCTAGT1124STESNAS2341102.431066CCGATTGCTGAGAGGCCTTCT1125PIAERPS2342102.4281067TTACTTCCAAACAACACCCAC1126LLPNNTH2343102.4241068GGGACTCTTAAGAAGGATGCG1127GTLKKDA2344102.4121069GCTCTTGAGAATCGGAGTCTG1128ALENRSL2345102.4081070ACCACCGGGAACTCCACGATG1129TTGNSTM2346102.3831071GTGTATGATAGTGCGCCTAAT1130VYDSAPN2347102.3661072CTACTATCTAAAGGGGACTCC1131LLSKGDS2348102.3461073TCTTACGCCATAAACCAATCA1132SYAINQS2349102.3351074GGAGGAGGGGAACGTTCCACG1133GGGERST2350102.3231075ATTCAGGTTAGTGGTAGTCAG1134IQVSGSQ2351102.3151076TATCCTGTTTCGCTTTCGCCG1135YPVSLSP2352102.3121077GAGTTGGGTAATAAGACGGCT1136ELGNKTA2353102.3111078TCGGGGGTAAACTTCGGAGTA1137SGVNFGV2354102.2871079GCGTGGAGTTCGCCGAGTGGG1138AWSSPSG2355102.2851080GGTGTGAATTATCATACTACG1139GVNYHTT2356102.2611081CTGATTGGGGAGCTTAAGATG1140LIGELKM2357102.2551082TATCTGAATAGTAAGCAGCTT1141YLNSKQL2358102.2121083ACTGTTGATAGGCCGATTGTG1142TVDRPIV2359102.1911084GTCAGCAAAACCAAAGACTCG1143VSKTKDS2360102.1841085CAAGCTGGGAACGCGCCAAGG1144QAGNAPR2361102.18061086CAAGACCAAACGAGCAACCGT1145QDQTSNR2362102.1771087GATACTACGTATCGGAATACT1146DTTYRNT2363102.1731088GGGACAACCGAAGTTAACAAA1147GTTEVNK2364102.171089GGGTTTACTAATACGAGTAAG1148GFTNTSK2365102.1521090GTGCAGAAGAATGATGTGCTT1149VQKNDVL2366102.141091AGCGTCAACAACATGCGACTC1150SVNNMRL2367102.13241092TTCAGTGCCGCCTTACCGTTA1151FSAALPL2368102.131093GACGTCCCAAACAACAAAAGG1152DVPNNKR2369102.1261094GGTGAGACTATGCGTCATAAT1153GETMRHN2370102.1191095ATTCGGACTTCTGTGATTAAT1154IRTSVIN2371102.1031096CCGCGTGCTCCTGGTCATAAT1155PRAPGHN2372102.1011097AGTGTTGCGCATCCTTTGTCT1156SVAHPLS2373102.1011098ATGACAATAACCGTCGAACCG1157MTITVEP2374102.0961099CCATTAAACGCGAACGGCTCC1158PLNANGS2375102.0941100AATAGGCAGCGGGATTTTGAG1159NRQRDFE2376102.0731101GATATTCATAATCCGCGTACG1160DIHNPRT2377102.0731102TGGATAGCAGGAAACCACTCC1161WIAGNHS2378102.071103TCTACTCATCATGCTGATCGT1162STHHADR2379102.0691104CCGGAATCCGCCGCCAAAAGC1163PESAAKS2380102.0581105CACTCCGACAAAGTCTCCTCA1164HSDKVSS2381102.0511106TCAAACAGCGCCGACGCGGGG1165SNSADAG2382102.0471107GAGTTTCAGAGGATTCGTGAG1166EFQRIRE2383102.0391108TCCGCGGGGATGACATTGGAC1167SAGMTLD2384102.0161109ACTCAAACTTCTACCTGGACC1168TQTSTWT2385102.0091110ACGACACTAACGCAAACGGAC1169TTLTQTD2386102.0031111GCCTCGAAAGGCTTCGGCCAC1170ASKGFGH2387101.9911112CCGGCTACGATGATTAGTGAG1171PATMISE2388101.9851113ACTGACTCATCTGCAGACTCC1172TDSSADS2389101.9811114TCAACCAGAAAAGAACACGAC1173STRKEHD2390101.981115GGTGATATTTCTTATAGGGTT1174GDISYRV2391101.9771116ATGGGGTATGTTGATAGTCTG1175MGYVDSL2392101.9531117CAAACCATCACCTCACAAATG1176QTITSQM2393101.9411118TCGATTGGGTATTCGCCTCCG1177SIGYSPP2394101.9391119TCATCCCCAGACTCGTACAGA1178SSPDSYR2395101.9211120ATTAGTCCGAGTGCTTCTAAT1179ISPSASN2396101.8551121TATCCGGCTGATCATCGGACT1180YPADHRT2397101.851122CACACCGGCCAAACACCATCA1181HTGQTPS2398101.8371123CAGACGACTATTCTGGCTGCT1182QTTILAA2399101.8371124GATGGTACGAGGCAGGTTCAT1183DGTRQVH2400101.8361125AGGAGTAGTCCTGCGACGAAT1184RSSPATN2401101.8291126GCGATGAGTCATACGTATAAG1185AMSHTYK2402101.8131127ATGGCGGCTCCGCCGGAGCAT1186MAAPPEH2403101.8021128GGTCCTAGTACTTCGGAGGCG1187GPSTSEA2404101.7941129CATAATCATGATAGGTCGTCT1188HNHDRSS2405101.78291130GTGGTCCCATCGACCCAAGCA1189VVPSTQA2406101.7811131ATTCCTGTGACTACTCGTAAT1190IPVTTRN2407101.7221132AACCAACTCGTACGCGGGACA1191NQLVRGT2408101.7171133GGGTTTGCGCTTACGGGTACG1192GFALTGT2409101.6961134TCTAAGGGTGGTGATATGGTG1193SKGGDMV2410101.6661135GCTCGACCAGGCCAATCTATG1194ARPGQSM2411101.62871136AAAGCAGACTACGAATCCTCC1195KADYESS2412101.6261137GGACCAAGTTCGCACATCGTT1196GPSSHIV2413101.6161138GAAGTTGTCAAAACCACGCAC1197EVVKTTH2414101.611139ACTTTGGATAATAATCATTCT1198TLDNNHS2415101.6041140ACGATTTATAATATGGGTCCG1199TIYNMGP2416101.5991141TCTACCATGAACACGATCACG1200STMNTIT2417101.5971142ACGCTGGCGCGGACTACTGAG1201TLARTTE2418101.5811143TTGATTTCTTCGCAGACTTCT1202LISSQTS2419101.5531144CAGACTGCGTCTGGTGATACT1203QTASGDT2420101.4971145GCGCATGGTGCTTTTCCGGTT1204AHGAFPV2421101.4951146GGGGAGACGCGGTCGACTGCT1205GETRSTA2422101.4941147AACAACTACGCCTACTCCGCT1206NNYAYSA2423101.4931148GAGGCTTATCAGACTGAGAAG1207EAYQTEK2424101.491149TCTCTAGCACACGCCGTAAGC1208SLAHAVS2425101.4851150ACGTATCAGTTGAGTGGGAAT1209TYQLSGN2426101.4521151ATGAGCGAAAGGTTGCGGATA1210MSERLRI2427101.4311152GGGTCGGGGAAAGACCCAGGG1211GSGKDPG2428101.431153TACAACAGCAACGCTTCTGTA1212YNSNASV2429101.4281154ACGAGGGGTGATATGGAGTTT1213TRGDMEF2430101.4241155GGAATCACCGGAAGCCCCGGC1214GITGSPG2431101.421156CAACACACCGCCCACCCCATG1215QHTAHPM2432101.4161157GATACGGCGAATCGTTCGACT1216DTANRST2433101.4071158TCGGCACACGACGCAAGACTA1217SAHDARL2434101.3871159CTTAATCATACTCTGGGGCAT1218LNHTLGH2435101.3851160GGGTTTGAGACGAGTAGTCCT1219GFETSSP2436101.3691161GGTACGAGTGCGGAGAGTCGG1220GTSAESR2437101.3661162CATGCTAATTATGTTGAGGTG1221HANYVEV2438101.3451163ACAACGAAACCGGTCGCGGAA1222TTKPVAE2439101.3381164TCGACCGCCGTTACTAACTCA1223STAVTNS2440101.3041165CTGGGGCTTGCTGGTCAGGTT1224LGLAGQV2441101.3041166GTGCTTAAGGGTACGTTTCCG1225VLKGTFP2442101.2981167ATGAATGAGCCTGGTAGGACG1226MNEPGRT2443101.2831168ACTTCTGATCCTTTGAGGAAT1227TSDPLRN2444101.2521169CGTGATACTAATACGGATAAG1228RDTNTDK2445101.2341170GAGTCTGATTTGCGTCAGCGG1229ESDLRQR2446101.2251171TCCGGAATGGCCGGCCTTTCC1230SGMAGLS2447101.2111172ATAGCAACAACGTCTGGGCGG1231IATTSGR2448101.211173ACGATTAGGAGTGAGGGTTTT1232TIRSEGF2449101.2021174GGTCTGTCTATTACTATTGCG1233GLSITIA2450101.1761175CCGCCTACTAATGGGCGTATG1234PPTNGRM2451101.171176CTACAAGACCGGGCAACGAAC1235LQDRATN2452101.1651177CTTAAATCGACCGGTGACCAC1236LKSTGDH2453101.1321178GATAATAATAATCAGGTTTAT1237DNNNQVY2454101.131179GTGCATATGGAGTCGTATGCG1238VHMESYA2455101.1111180GACCAAATAGGGCACGGAACA1239DQIGHGT2456101.1061181GGGACGGGGCCGCATGGTACT1240GTGPHGT2457101.07121182ATTGGGAATAATACTGGTCTT1241IGNNTGL2458101.05291183TTAAACGCAGAATACACCAAC1242LNAEYTN2459101.0471184GTGACGTCGTCTGCTAGTGGT1243VTSSASG2460101.0271185ACGCATGTTGCTAAGCCTGAT1244THVAKPD2461101.0171186CCGATGAACAAAGACATACTG1245PMNKDIL2462100.99061187CTTAGTTTGAATATGAATGAG1246LSLNMNE2463100.991188GTCGGCAACTCAAGCACTCAC1247VGNSSTH2464100.991189GGCCACGGAAGTGACTTGACC1248GHGSDLT2465100.95761190CTTACACAAAACCCAACGAAC1249LTQNPTN2466100.9341191CCGAGTGATCATATGCGGACT1250PSDHMRT2467100.88491192CCTGATAGTCGTTTGGCGGCT1251PDSRLAA2468100.8431193TGGGGTAGTGAGGGGACGATT1252WGSEGTI2469100.841194AAACCGACAAACGACTCGTAC1253KPTNDSY2470100.8211195AACCGCGGAACAGAAGTTTAC1254NRGTEVY2471100.81471196CACGTGATCACAACAAAAGAC1255HVITTKD2472100.78961197ATTGTGTCTAATCCGCCGGCG1256IVSNPPA2473100.761198ATGCGTAACGACCAACAACTT1257MRNDQQL2474100.75031199TTTCAGCGTGATGTTGGTCAT1258FQRDVGH2475100.73921200GCCAACGACAACACCAAACAA1259ANDNTKQ2476100.73641201TCTGTTCCGCATGCGGGGGAT1260SVPHAGD2477100.72761202AATGCTACTCCGCCGAATCAT1261NATPPNH2478100.66781203TCAGAACACACATCAGTTCTA1262SEHTSVL2479100.641204GCCATGTCCCAAACGGACATC1263AMSQTDI2480100.6281205CCTAAGGCTCCGCTTAATAAT1264PKAPLNN2481100.6271206ACCAACAACTTACTCGCACAA1265TNNLLAQ2482100.551207CAGCGTCAGGGTTCGGGGGTT1266QRQGSGV2483100.53181208CGCAGTGACACCACTAACGCC1267RSDTTNA2484100.511209GAGGCTGATAAGAATGGTGTT1268EADKNGV2485100.3861210ATGCTGGGGGGTTTTGCGCAG1269MLGGFAQ2486100.36221211ATGACACACCTCAGCACAGAC1270MTHLSTD2487100.2671212GTTTTGTCTGATAAGGCGTTT1271VLSDKAF2488100.2311213ACACCCTCCGGTACCATAAAA1272TPSGTIK2489100.221214ATTATTCTTATGGGTCAGAGT1273IILMGQS2490100.2131215CTTTCGGGGGGTGAGACTCTT1274LSGGETL2491100.1541216ACCGACGGCGCCCTGGGTTAC1275TDGALGY2492100.1291217GGGAATAAGGCTGCGCTGACG1276GNKAALT2493100.066TABLE 2MHCK7 Results mRNA Second Round of Capsid Variant Selection inC57BL6 mice-score capped at 100VariantSEQ IDSum of muscle mRNAIDNucleotide SequenceSEQ ID NO:aaNO:score capped at 1001AGAGGAGACTTGACAACCCCA2494RGDLTTP3737576.122CGGGGTGATCTTAATCAGTAT2495RGDLNQY3738496.413AGGGGTGATCTTTCTACGCCT2496RGDLSTP3739475.9094CGGGGTGATCAGCTTTATCAT2497RGDQLYH3740460.5785CGAGGAGACACCATGAGCAAA2498RGDTMSK3741439.7716AGGGGGGATGCGACGGAGCTT2499RGDATEL3742429.747AGAGGCGACTTATCCACACCC2500RGDLSTP3743429.1828CGCGGCGACATGATAAACACC2501RGDMINT3744397.629AGGGGCGACCTGAACCAATAC2502RGDLNQY3745388.41710CGGGGGGATACTATGTCTAAG2503RGDTMSK3746352.26811CGGGGTGATCTTACTACGCCT2504RGDLTTP3747320.04212AGGGGCGACCTCAACGACAGC2505RGDLNDS3748315.61513GCAAACCCCAACATACTAGAC2506ANPNILD3749302.0214CGAGGCGACACAATGAACTAC2507RGDTMNY3750285.33215ATGAGTAATTTGGGGTATGAG2508MSNLGYE3751270.7416TACACCTCTCAAACCAGCACT2509YTSQTST3752256.54417CTCGGAGGAAACAGCAGGTTC2510LGGNSRF3753255.42518CAAAGCCAAGCGATACAACTA2511QSQAIQL3754254.19119AACACGTACACACCGGGAAAA2512NTYTPGK3755239.56520GGGGCGGAAGCGGGCCGCCAA2513GAEAGRQ3756237.282921GAACACGCTACAGCAAAACAA2514EHATAKQ3757236.82622GCGGCACAACTCGTCAGTCCA2515AAQLVSP3758225.03423GATCAGACGGCTAGTATTGTT2516DQTASIV3759224.83224GTTCAAACCCACATAGGAGTC2517VQTHIGV3760224.30625TCTTATGGTAATACTCATGAT2518SYGNTHD3761224.2626ACCTCCACGGCTTCAAAACAA2519TSTASKQ3762221.61727TTGGTGACTCATGAGCGGATT2520LVTHERI3763219.22728ATGGATAAGTCTAATAATTCT2521MDKSNNS3764216.63829CGTGGTGATATGTCTCGTGAG2522RGDMSRE3765214.70830CGCGGTGACGTGGCAGAAATA2523RGDVAEI3766212.96731GGTGGCGAAAACAGAACCCCA2524GGENRTP3767210.432GCTGGGCATCAGCAGCTTGCT2525AGHQQLA3768210.174633CGTCTTAATAGTAGTATGAAT2526RLNSSMN3769209.44934TATTATGAGAAGCTTAGTGCG2527YYEKLSA3770209.26335GAAGCGTCCAACTACGAACGA2528EASNYER3771209.0936TTCCAAACTGACACGCACCGA2529FQTDTHR3772208.9537AACAGTTCCCAATGGCCCAAC2530NSSQWPN3773208.63838GATGGTAAGACTACGTCTAAT2531DGKTTSN3774207.63839GCTGTGCATGCGACTAGTAGT2532AVHATSS3775205.95240AAAACACTCCCCGGCAGGGAA2533KTLPGRE3776205.92641ATACTGAAATCCGACGCACCA2534ILKSDAP3777204.52342AGTACGAATGAGGCTCCTAAG2535STNEAPK3778204.52243TTTGATAGTGCGAATGGTCGG2536FDSANGR3779203.99644ATGGACGCTGCGTACGGTAGT2537MDAAYGS3780203.40145AACAAAGACCACAACCACCTG2538NKDHNHL3781202.87846GGTCAGTATAGTCAGACGCTT2539GQYSQTL3782202.55347GAAGCATTCCCGCGAGCGGGC2540EAFPRAG3783202.27548GAACACACTCACTTAAACCCG2541EHTHLNP3784201.95949ATGCAACGCGAAGACGCGAAC2542MQREDAN3785201.52350CTAACCGGCTCTGACATGAAA2543LTGSDMK3786200.37651CGAGTAAACAACGACGCAATA2544RVNNDAI378720052CGTGGTGACCAAGGCACACAC2545RGDQGTH378820053ATTAATATTAGTAGTGATTTT2546INISSDF378920054AATAATGATAATGGTTTTGTT2547NNDNGFV379020055TTCATCGCTAACACTAACCCA2548FIANTNP379120056GGACTGCACGGCACCAACGCA2549GLHGTNA379220057AAAACCATCGACATAGCACAA2550KTIDIAQ379320058TCGAGTGATTCTCGTATTCCG2551SSDSRIP379420059TCTACATCTCCGGTTAACAGC2552STSPVNS379520060GCCAGCATGCCCTCTGTAGAC2553ASMPSVD379620061GGTCATAATATGGCACAGGCG2554GHNMAQA379720062CACAACAAACCAAACGGAGAC2555HNKPNGD3798197.85163TACAGGATGGAAACGAACCCA2556YRMETNP3799197.4664CTTGGGAATGTGGTTCATCCG2557LGNVVHP3800197.38365GTAACGGCACACCAATTATCC2558VTAHQLS3801196.09566ACTATGGTAGAAGTACTGCCA2559TMVEVLP3802195.58667ATCAAAGGGTCTGGGTCGCAA2560IKGSGSQ3803195.29668ACTAATGGGGGGTCGCTTAAT2561TNGGSLN3804193.95969CTCGGAGGAAACAGCAGGATC2562LGGNSRI3805193.2170AGGGGTGATGCGGCGAATAAG2563RGDAANK3806193.1671GCGTTAAACGCCCAAGGGATC2564ALNAQGI3807192.98672GCTGAGCATGCGACTAGTAGT2565AEHATSS3808192.5973TACTTGACCACCGGTACTGCC2566YLTTGTA3809191.52174GCGGAGGCTCAGACGCGTGTG2567AEAQTRV3810189.89975GCTGAGCAGGGGCTGTCTTCG2568AEQGLSS3811188.9476CTGATTGTTACTCAGCATGTG2569LIVTQHV3812188.58877TCTAGTTATCAGTCTGGGCTG2570SSYQSGL3813188.478GCTACGGTTTATAATGAGTTG2571ATVYNEL3814188.1879CATGATACGGTTGGGGAGAGG2572HDTVGER3815187.26980CGTGGGGATTTGAATGATTCT2573RGDLNDS3816187.2581CATGATATTAGTCTGGATCGT2574HDISLDR3817186.6582ACAGAACAATCTTACTCACGA2575TEQSYSR3818186.23783TGGTGAGGGGCTGAGTTTGCC2576W*GAEFA3819186.184GCTGTGCATGCGACTAGTAGA2577AVHATSR3820185.985ATTGAGAGTAAGACTGTGCAG2578IESKTVQ3821185.81886ACGAATGTTAGTACGCTTTTG2579TNVSTLL3822184.36587CCACCCAACGGCAGCAGTAGA2580PPNGSSR3823183.25888CCCTCTACACACGGCTACGTA2581PSTHGYV3824183.23589ACTGCGGCTAGTACTGCGAGG2582TAASTAR3825182.45290TACAACGCAGGCGGAGAACAA2583YNAGGEQ3826182.1491ACCCACAACCAACGTGAACTG2584THNQREL3827181.98992ACCTTCACGGTCGACGGTAGA2585TFTVDGR3828181.72493CACTCCAGCCCCGGGTCGTCA2586HSSPGSS3829181.33194AGTACGAGTGGTTATAATACT2587STSGYNT3830180.37295TCTGAGAAGCTGACTGATAAG2588SEKLTDK3831180.17496GGGAGGAACACAAGTAACTTG2589GRNTSNL3832180.15697ACCGGAACAGCGATCTCCCGA2590TGTAISR3833180.14898TCTATGCAGGATCCTTCTTTG2591SMQDPSL3834179.22299ACTCGGAGTGATATTGGTGTG2592TRSDIGV3835178.75100ACGCAGAATCATCAGTTGTCT2593TQNHQLS3836178.39101TTTGTTGATAATAGGCAGCCT2594FVDNRQP3837178.388102AGTTTGAATTCTTCGAGTACT2595SLNSSST3838177.704103AAGGCGGTTTCGGAGATTATT2596KAVSEII3839177.335104GGTACGAGTGATAATTATAGG2597GTSDNYR3840176.93105ATGTCTAGCCACACCGTCCAA2598MSSHTVQ3841176.741106AGTATCACCCACAGCAACACC2599SITHSNT3842176.571107GTTCAGACTAGTACTGGTGCT2600VQTSTGA3843176.399108CGTGGTGATATGACTCGTGCG2601RGDMTRA3844176.36109ATTGGTCTGCAGAATTCTACT2602IGLQNST3845176.164110AGTGCGGATCGTGATAATAAG2603SADRDNK3846173.544111TACTCTCAATCCATAAAAAAC2604YSQSIKN3847172.725112CGCTCGTTGGACAGCGGGATG2605RSLDSGM3848172.632113GCTGTGCCTCAGTCTCTGCCT2606AVPQSLP3849172.274114GCGAATGATAGTATTAAGCTG2607ANDSIKL3850172.18115AATGGTAATATTTATCCGTCT2608NGNIYPS3851171.981116GGGCAAACAAACGCAGTACAC2609GQTNAVH3852171.5364117CAAGGAGACCTACGTGGCTCG2610QGDLRGS3853171.042118GTTAAGGCGAGTGCTGGGGTT2611VKASAGV3854170.5608119ATCGCGTCAACGTGGAACATG2612IASTWNM3855170.52120AACTCGGCTGAATCCTCGAGA2613NSAESSR3856170.31121GTCTTCACGGGCCAAACTGAA2614VFTGQTE3857170.216122TTTGGTACTTCTTATACGACT2615FGTSYTT3858169.719123GCGGTTAATGAGACTAGGCTT2616AVNETRL3859168.767124GGTCGGACGGATACTCCTAAT2617GRTDTPN3860168.735125AACGACCGACCGCTTGCCAGC2618NDRPLAS3861168.71126GCTTATCAGCTGACTCCGGCT2619AYQLTPA3862168.579127ATGGGTGAGATGGGTAATATT2620MGEMGNI3863168.24128GCGGACATGCAACACACCGTA2621ADMQHTV3864168.055129GCGGTTGTTCTGAATAGTAAT2622AVVLNSN3865168.021130TTTCGTGATGGTCAGGGTATG2623FRDGQGM3866167.193131AAATCGACATCAAACATCGAA2624KSTSNIE3867166.8294132ACCCAAGCCTTCTCCCTAGGC2625TQAFSLG3868166.751133TGGTCGAGAACTGGAAACACC2626WSRTGNT3869166.483134AGCACAAACACCGAACCTAGG2627STNTEPR3870165.304135GAGAATAGTGATTTGTCTTAT2628ENSDLSY3871165.08136ATAGACGAACGTTCCTCGATA2629IDERSSI3872165.02137GATGTGCATTCGAGTATTCCT2630DVHSSIP3873164.85138ATAAGCGGTTCCACTACACAC2631ISGSTTH3874164.788139TGGCAAACCCAAGTCACTACA2632WQTQVTT3875164.759140AACATGGGTCCAATGGGCCGG2633NMGPMGR3876164.41141GTTACCCAATCGTCCACGCTA2634VTQSSTL3877164.175142ATTGATCGTAGTGCTAGTTTG2635IDRSASL3878164.016143TCTCATAGTATTACGGGTCTT2636SHSITGL3879163.92144AAAGCGGGACAACTAGTGGAA2637KAGQLVE3880163.845145AGCGGTGTATCAGAAGGAAAC2638SGVSEGN3881163.413146ACGCTTACATTATCTACCCTC2639TLTLSTL3882163.242147GCCCACAACAAACACGAAAGT2640AHNKHES3883162.975148CACAACAACAACCTGCAAAAC2641HNNNLQN3884162.633149TATAATGAGTCTTCGAATGCG2642YNESSNA3885161.92150CGTGAGCAGGCTGCGGAGAGG2643REQAAER3886161.523151ACTCAGTATGGTACTCTGCCG2644TQYGTLP3887161.32152CATCCTGGGAATAGTTCTGTG2645HPGNSSV3888161.2153AGTTCTAGGGAGGTGAGTCCG2646SSREVSP3889161.091154GCAAACTCCACAAGCCAATGG2647ANSTSQW3890160.842155CGCGACATGATCAACTCATCA2648RDMINSS3891160.83156GCATTGCCCAGCGGCGCACGA2649ALPSGAR3892160.765157CCTGGCACCAGTGGATCCCGA2650PGTSGSR3893159.7012158TGGAACGGAAACGCCACACAA2651WNGNATQ3894158.413159GGTAAAGCAACCTTAGTCCTC2652GKATLVL3895158.386160TACACCAACGGGGGCCACCTA2653YTNGGHL3896158.346161TCACAATACAACGGAACGCAA2654SQYNGTQ3897157.872162TATTCTAGTGAGAGTGCTTAT2655YSSESAY3898157.56163GTTAAGGCGGGGGTGGCTGAT2656VKAGVAD3899157.534164ACGATGGGGACGGTGCAGATT2657TMGTVQI3900157.384165GGTGTGGCTGGTGCGGTGGTG2658GVAGAVV3901156.882166TATGATAAGACTTTGAGTGTT2659YDKTLSV3902156.791167CATGGGAGTGCGTATTCGCAG2660HGSAYSQ3903156.45168ACGGCTAATATTATGAGTAAG2661TANIMSK3904155.935169TTTTCGCGGGAGACGCTGGCG2662FSRETLA3905155.888170TTGAGTGGTGCTGGTAGTCAG2663LSGAGSQ3906155.554171AGTAATGCGAATCAGATGAGT2664SNANQMS3907155.28172TCGGTCCTTTCGCCTTCGAAC2665SVLSPSN3908154.987173GATAATGTGCATGGGCAGGTG2666DNVHGQV3909154.72174GACGGACGAGAATACGCCTCG2667DGREYAS3910154.33175ATTTCGAATCAGATTAAGATG2668ISNQIKM3911154.262176GGTCGAGACAACCAACACGTA2669GRDNQHV3912154.136177CGTAATCATGAGACTGGGGCT2670RNHETGA3913153.8093178AGTGGGAGTGGTGCGAATATT2671SGSGANI3914153.55179TCTATGTCTGATGGGCTTCGG2672SMSDGLR3915153.296180AAGGAGAGTAGTGCTATGGAG2673KESSAME3916153.04181GCTAATGCTAGTACTAGTCTG2674ANASTSL3917152.807182AGTGCTTCTGGTTATTTGGTT2675SASGYLV3918152.79183GATACTACTCAGAAGCCTCAT2676DTTQKPH3919152.687184CTAATACGAGGTTCCATGGAA2677LIRGSME3920152.55185GACCGCACCTACTCAAACACA2678DRTYSNT3921152.447186GCTCTTGGGCATCAGGGGAAT2679ALGHQGN3922152.38187GCTAATCATACGTCGCAGGAG2680ANHTSQE3923152.056188GAGAGGGGTTTGAATACTAAT2681ERGLNTN3924151.4189ACTGTTGGTGGTAATCATCAT2682TVGGNHH3925151.384190CCGAGTGATAGGACTACTTAT2683PSDRTTY3926151.365191TCCAGGCAAGAAAACTTCTCC2684SRQENFS3927151.22192AATAAGACGACGATGGAGTTT2685NKTTMEF3928151.16193AAACACACAGAAAACGGGACC2686KHTENGT3929150.985194GAAACCGGAGCTATGACCTCT2687ETGAMTS3930150.803195GGTCATAGGGATTCGGGTGGT2688GHRDSGG3931149.991196AGAAACGCCGAAGGCGGATTG2689RNAEGGL3932149.919197GGGCAGCGTACGACGAATGAT2690GQRTTND3933149.903198TATAATGATGCTCTTAGGCCG2691YNDALRP3934149.88199GGGTATGCGACTACGGTTCAG2692GYATTVQ3935149.694200ATAGGGGGAGGCATAGGAAAC2693IGGGIGN3936149.622201GTGGCGGTGTCTAATACGCCT2694VAVSNTP3937148.5637202CTTGCGAATGGTATGACGGCT2695LANGMTA3938148.449203ATTTCTGGGTCGTCGTCTCTT2696ISGSSSL3939148.328204TCTAATGTTCATGTTGTTAAT2697SNVHVVN3940148.32205GTGGAGACTTCGCGTCTGTAT2698VETSRLY3941148.302206TCGAACGCAGACATCCTCGCC2699SNADILA3942148.08207AACAACGTAAACCCGTACTCG2700NNVNPYS3943148.016208ATAAGTGTAGGTGTGTCCGTA2701ISVGVSV3944147.84209TCCGCAAACAACATAGCCCCC2702SANNIAP3945147.813210GGTGTTCAGATGACTGCGGGG2703GVQMTAG3946147.527211CGTTACATCGCCAACCAAACA2704RYIANQT3947147.305212ACCACCGAAAGTCTACACCTT2705TTESLHL3948146.899213GGCTACCAAGACAAAACACGA2706GYQDKTR3949146.705214GCTTCGCGGCCTGCGGCTCAG2707ASRPAAQ3950146.364215TCTATTCAGGAGCTGTTGAGG2708SIQELLR3951146.287216ACTGTGCGTTCGCCTCAGCAG2709TVRSPQQ3952145.74217GCGGTTCTTGGTGGTAGTAAT2710AVLGGSN3953145.633218ATGAGTACGGTTCTTCGGGAG2711MSTVLRE3954144.928219ACTTATGGTATTACTCATGAT2712TYGITHD3955144.751220GATGCGAATGCGGGTACGAGG2713DANAGTR3956144.597221TTCAACGGGTACGTCATGGCA2714FNGYVMA3957144.536222ATTAATAATTTTAATACTCTG2715INNFNTL3958144.08223GTAGCCAACGAACGCCTACCG2716VANERLP3959143.64224ACTAATTCTAATCAGGGTTCG2717TNSNQGS3960143.617225GCGACGCTGAATAATAGTTAT2718ATLNNSY3961143.512226AAAAACGCTCAAATAGACCTA2719KNAQIDL3962142.66227CCTGCTACGCTACACCTGACA2720PATLHLT3963142.552228TTAGGATCGAGCACAGTATCG2721LGSSTVS3964142.325229AATTGGAATTCTGAGGGTACG2722NWNSEGT3965142.257230CCAACAAACAACTTAAGTATG2723PTNNLSM3966141.91231GCGCTTAAGCCGAATTCTACG2724ALKPNST3967141.737232ATGGTGAATTCGGAGAATACT2725MVNSENT3968141.624233AGTATGGATGCTCGGTTGACG2726SMDARLT3969141.6234AATAATGTTGTTAGGGATGAT2727NNVVRDD3970141.597235ACAAGGGACCAAAGGTCTACA2728TRDQRST3971141.592236GCTGACATCCGGAACGACAAA2729ADIRNDK3972141.468237ATGCGGGATAAGATTAATCCG2730MRDKINP3973141.468238CCGACTCCTAATGAGCATATG2731PTPNEHM3974141.465239GGATACTCACACAACTCCGAC2732GYSHNSD3975141.448240CTTCGGGATGGGATTGCTTCT2733LRDGIAS3976141.105241ATGAACCAAATGGGCGGCCTG2734MNQMGGL3977141.089242TCTTCGCCTACTAAGGGTACT2735SSPTKGT3978140.803243TATTTGGATAATCCGTTGACG2736YLDNPLT3979140.516244GTCATGCAACGATCTGCACAA2737VMQRSAQ3980140.2245TCTCTGCAACTCACAGCGGGT2738SLQLTAG3981140.161246GTGGGGTCTGGGGGTTATAAT2739VGSGGYN3982140.139247GATCGTCCGAATAATGTGTCG2740DRPNNVS3983140.036248TTGACTGAGAAGGCTTCTATT2741LTEKASI3984139.945249ACCACAAAAACGACATCTATG2742TTKTTSM3985139.556250CGTTTGGACCTGCAAGTCCAC2743RLDLQVH3986139.528251ACTCATGTGATTGGGGCTGTG2744THVIGAV3987139.34252ACCCTGACACACCTAAACCCA2745TLTHLNP3988139.142253ACCTCAATATCGTCGCAAAGC2746TSISSQS3989138.884254TACCACACCCACCAAGTCGCA2747YHTHQVA3990138.871255ATGCAAGGGCTTAACAACATG2748MQGLNNM3991138.848256GGTAGTGCGAGTAATAGTGGT2749GSASNSG3992138.841257GCGAATACTACGGGGCAGGTG2750ANTTGQV3993138.7122258AGCGTTGTCAACACCAACATC2751SVVNTNI3994138.699259TCTAATAATCTGAATCAGGAG2752SNNLNQE3995138.543260ATGAATGGGAGTGGGATGCAG2753MNGSGMQ3996138.484261ATAAGTCACGACCTTAAATAC2754ISHDLKY3997138.458262ACGGTTAATGCGGATGGGTCG2755TVNADGS3998138.21263AATCATATTAGGAATCCTATG2756NHIRNPM3999138.143264AGTACGCGGGTTACTCTGGAT2757STRVTLD4000137.85265GCTATGGGAGCACTCGTGCAC2758AMGALVH4001137.838266GCGCAAGCCATGTCAAACAGC2759AQAMSNS4002137.76267AATGCTAATGGTATGAATACT2760NANGMNT4003137.343268TTGACGCTTCCTAGTGCTAAT2761LTLPSAN4004137.264269TACCAAACGGGAGACAAAGAC2762YQTGDKD4005137.017270AGACGGGAAGAAAACGTCAAC2763RREENVN4006136.962271GGAACTACCACGGCAGTCGCG2764GTTTAVA4007136.8811272ACGGCTGGTGGGGAGCGTGCG2765TAGGERA4008136.6273GCCGGTAACGAACCTAGACCC2766AGNEPRP4009136.593274GCAAACAACACAGCCAACAGT2767ANNTANS4010136.498275CATGTGAATAGTAGGGATCTT2768HVNSRDL4011136.187276ACATACCAACTTTCCGGCAAC2769TYQLSGN4012136.059277CGGGGTGATTCGATGGCTCGG2770RGDSMAR4013135.8517278TTGAATAATTCTGCGACTGTT2771LNNSATV4014135.76279CTACACGCTAACAACGAACGG2772LHANNER4015135.723280ATGGGTTCTACGACTGGTGTG2773MGSTTGV4016135.16281GTAGTTGCAGGGCACGCAATG2774VVAGHAM4017135.1261282GGCAACGAAAAACCATCAGGG2775GNEKPSG4018135.016283CGTGGTACGGAGGGGACGCCG2776RGTEGTP4019134.8972284TGGTCCCCCGGACCCGAAGCC2777WSPGPEA4020134.66285ATTAATGTGAATCAGATGGCG2778INVNQMA4021134.472286CGGTCGGACGTTATGCAAAGT2779RSDVMQS4022134.362287AGGGACGTAAGTACAAAAGAA2780RDVSTKE4023134.36288AAAAAGTCACCCAGACTTGAA2781KKSPRLE4024134.35289ACGAGCAACACAATGTCAGAC2782TSNTMSD4025134.345290TCTAAAGGAAACGAACAAATG2783SKGNEQM4026134.224291GGTTACGCTACGACCGTGCAA2784GYATTVQ4027134.185292GGATACATGTCTAACGTCATA2785GYMSNVI4028133.922293GTGACTGTTAGTCTGGATGGG2786VTVSLDG4029133.879294ACGAATAATTTGCTGGCTCAG2787TNNLLAQ4030133.517295GCGCAGACGACGGGGTATACG2788AQTTGYT4031133.295296AGTAAGTCGACTGAGATTATG2789SKSTEIM4032133.249297TCTGCGATGCACACATTAGTC2790SAMHTLV4033133.226298GCTGGGGTGCGTGAGTCGTTT2791AGVRESF4034133.15299CAAGGCAACTCAATGGCGTCC2792QGNSMAS4035132.82300AAAAACCCGAGTGTCCAAGAA2793KNPSVQE4036132.519301CCCATAACACGGGAATCGGGA2794PITRESG4037132.424302AGCCGCTCGGCAGAAATATCG2795SRSAEIS4038131.747303AACGACATCCCCACACGAGCC2796NDIPTRA4039131.424304GCATACGGATCGTCCGGAAGA2797AYGSSGR4040131.375305CTTCATGGGAATTTTAGTCAG2798LHGNFSQ4041131.002306GCATCCAACGGGCAAGTTAAC2799ASNGQVN4042130.736307CAGAAGGGGACGGTTACTCTG2800QKGTVTL4043130.375308AACTCTAGTAACACTGGTTGG2801NSSNTGW4044130.26309ACGTATCAGCATCAGGGTCCG2802TYQHQGP4045130.231310GACGGGGTCGCACACCGCTCA2803DGVAHRS4046130.216311GACGGGCTCACGCTGGAACGC2804DGLTLER4047130.09312AGGGGTGATCTATCTACGCCT2805RGDLSTP4048130.02313ATTAATGAGATTGGTAGGATG2806INEIGRM4049129.944314CCCCAATGGGGAACTGACCCG2807PQWGTDP4050129.94315AAGCAGGTGGCGCATATTGAT2808KQVAHID4051129.831316AATACTTTGCAGAATAGTCAT2809NTLQNSH4052129.563317TGGAGCCAAGGGAACACAGCG2810WSQGNTA4053129.438318AACGAAACGCACGTACCTAAA2811NETHVPK4054129.35319GTAACGAACGAATCCCGCGCC2812VTNESRA4055129.059320CCCGAAGGCCACATGCAAGAC2813PEGHMQD4056129321TTGGATTCGACTAATTCTAGG2814LDSTNSR4057128.63322CAGTCGATTGGGCATCCGGTG2815QSIGHPV4058128.17323GTCCTGGTTAACGTACACAAC2816VLVNVHN4059128.078324GTGCATAATCCTACTACTACG2817VHNPTTT4060127.727325GGGGATAAGGCGAGTTTGGCG2818GDKASLA4061127.698326CTAAACGAATCCCGAGCGTCG2819LNESRAS4062127.597327GGTTTTCATATTAATGGTGAG2820GFHINGE4063127.526328AGTGTTAGTTCTGTGGTGTTG2821SVSSVVL4064127.19329CTTTCGACTACTTCGACGAAG2822LSTTSTK4065127.153330ACTAATACGCAGAATAATCCG2823TNTQNNP4066127.089331ACTAATCTTGCTGTTACGCTG2824TNLAVTL4067127.0208332ATGTCGGATCGTACTTCTGAT2825MSDRTSD4068126.91333TCCGCGCAATCTTTCGTAGTT2826SAQSFVV4069126.906334ATGCACACAAGTAGACCCCCA2827MHTSAPP4070126.861335ATGTCTAGCCACACAGTCCAA2828MSSHTVQ4071126.79336AGGGATACGGCTAAGGGGGTG2829RDTAKGV4072126.773337GCGTTAAAATCCGACAGCGCC2830ALKSDSA4073126.73338CAATACGACGCCAGCCGACAA2831QYDASRQ4074126.66339TTAGCCGACTCAAACAGCAAA2832LADSNSK4075126.48340TTTCAGTTGGCTAGTAATCCG2833FQLASNP4076126.372341AACTCTGTCGTAGGGAACATC2834NSVVGNI4077126.308342AGGTATGAGAGTACTAGTGCT2835RYESTSA4078126.21343GCGGATCATAATCATATTGCT2836ADHNHIA4079126.21344GTAGGCGACCAATCCCGCCCG2837VGDQSRP4080126.106345TTCAACGAAACTGCCGGGCGA2838FNETAGR4081125.693346AGCAACTCGTACTTACTCAAC2839SNSYLLN4082125.52347CGAGGCGACACAAAGAACTAC2840RGDTKNY4083125.09348ACGACTACTACTATGGCATAC2841TTTTMAY4084125.064349CGACCCCCGAACGAAAACAGA2842RPPNENR4085124.7157350TGCGCCAACATGACCAACGGC2843CANMTNG4086124.6351AATCGGTCGGATAGTTTTGCG2844NRSDSFA4087124.567352AATCTTTTGACTTCGTCGCCT2845NLLTSSP4088124.54353AACTCCAGGGAAATGGGTGTA2846NSREMGV4089124.539354ATGGGGAATCAGAGTGGTGCG2847MGNQSGA4090124.506355ATGCTCACAGAAACCAAAGCA2848MLTETKA4091124.3356CAAAACATCAAAAACATGACA2849QNIKNMT4092124.1357ATGAGTACGGTTCTTCGCGAG2850MSTVLRE4093124.05358GACCGTGCCCAAAACAACGAA2851DRAQNNE4094123.95359CATACGCAGTCGACGGGTTAT2852HTQSTGY4095123.943360ATGAGTGTGGGGAAGGTTTAT2853MSVGKVY4096123.919361GCCGGAAACTACCAATCATCA2854AGNYQSS4097123.855362AGAAACGAAAACGTAAACGCT2855RNENVNA4098123.777363GACACCCACCACACATCCAGT2856DTHHTSS4099123.766364ACTAGCTCCCCTGTTCTACAA2857TSSPVLQ4100123.762365GTGGGCCGTGACGCAGAAGCT2858VGRDAEA4101123.74366AACATGGAAAGAGGATCGCAA2859NMERGSQ4102123.646367GACAGACAAACAGGCCAAAAA2860DRQTGQK4103123.6413368GTCTTCCGGGAAGGCATCGTG2861VFREGIV4104123.54369TCCGCAAACAACATAGCCACC2862SANNIAT4105123.32370GTATCAGAAGGACAACGAATC2863VSEGQRI4106123.005371CACTACGGTAACAAAGACATA2864HYGNKDI4107122.894372GATGTTTTGCTTAAGAATTTT2865DVLLKNF4108122.89373CACACGGTTCAAATACGCGAA2866HTVQIRE4109122.8082374ACATCAGCACTAGCACACCAA2867TSALAHQ4110122.78375ATCCCAACCGGCCAAACTAGC2868IPTGQTS4111122.752376CGCAGCGACAAAGGAACGTTG2869RSDKGTL4112122.7439377AATGGTCTTACGGTTCAGCGG2870NGLTVQR4113122.718378ACGGTTGAGGGTTCTTATCCG2871TVEGSYP4114122.67379ACTAGCCACTTAGTACTTGCA2872TSHLVLA4115122.653380AATCATAGTCTGTCGGAGCAT2873NHSLSEH4116122.5381TTAACAGGCATGAACAGAGAC2874LTGMNRD4117122.335382AGTCACAACGCTGGGGTCGCC2875SHNAGVA4118122.285383GCGCACCAAACCGCCGGGCCA2876AHQTAGP4119122.22384AATTCTCATGATTTGAAGTAT2877NSHDLKY4120121.99385ACTACAATGAGTACCGGTCAA2878TTMSTGQ4121121.98386GGGTTCGGGCACGTGCCCGAA2879GFGHVPE4122121.974387ATCACCGCCGCGTCACCGCAA2880ITAASPQ4123121.868388GTTAAGGCGAGTGCTGGGGAT2881VKASAGD4124121.75389AGTATCACACACAGCAACACC2882SITHSNT4125121.75390CATAATAATAATATGCTGAAT2883HNNNMLN4126121.659391CCCAAAACTCTAACTTCGACA2884PKTLTST4127121.479392ATAACCGGCAACACCGTCGGA2885ITGNTVG4128121.385393CTCGGAAACCACTACACACCC2886LGNHYTP4129121.38394TCGTTTACTAATACGAATCCT2887SFTNTNP4130121.294395ACGTTGGATCGGAATCAGACT2888TLDRNQT4131121.25396ATCTCTACGCAAAGACCGCAC2889ISTQRPH4132121.2071397ACATTCACTACTCTGGGCAAA2890TFTTLGK4133121.179398GAGAAGCCTTCTCTTGTGATG2891EKPSLVM4134120.927399CACATCGAAACCAACACTTCG2892HIETNTS4135120.834400GGTACGAAGGATATTCTGATT2893GTKDILI4136120.792401GCGACTTTTAGTCATGCTGGT2894ATFSHAG4137120.788402GCCAACGGCATATTCCAACCG2895ANGIFQP4138120.646403CTTAATGTGAATACGCTTAAT2896LNVNTLN4139120.55404ACTTCTGCTAGTGAGAATTGG2897TSASENW4140120.5405CTTCTTCAGGGTGCGACTAAG2898LLQGATK4141120.358406GCTCTTGAGACTACTCGTGCT2899ALETTRA4142120.26407TTAACGGGACAAAACGAATTC2900LTGQNEF4143120.24408ATTTCTCATGATTTGAAGAAT2901ISHDLKN4144120.191409GCACAATACAACAACGGCGTA2902AQYNNGV4145120.19410ACGACGTCTGTGGAGAAGACT2903TTSVEKT4146120.106411GGTACGTCGGCTATTATGCCT2904GTSAIMP4147120.093412CAGCTGCAGGGGACTGAGGCG2905QLQGTEA4148120.02413GCCTTAAAATCCCAAGAACCA2906ALKSQEP4149120.007414TCTAACAGCAGTGTTGCGGTA2907SNSSVAV4150119.89415AATCATGGTCGTGCTATTGAT2908NHGRAID4151119.776416GATACGTATAATAGTAATACT2909DTYNSNT4152119.6417ACATTCCACCAAGCGGTCAAA2910TFHQAVK4153119.54418TGGCATACTGGTGTGTTTCAG2911WHTGVFQ4154119.48419AGGGGTGATCTTTCTACGCCA2912RGDLSTP4155119.47420ATGCTTAGTCAGGTTCTGACG2913MLSQVLT4156119.414421GAAAACGAAAAACGAGAAAGC2914ENEKRES4157119.391422ATTTCGAGTTATGATGGTAAT2915ISSYDGN4158119.38423ACTCGTGGCGACATGGAATTC2916TRGDMEF4159119.36424AATGTGCAGAATGTGCCTGGG2917NVQNVPG4160119.3363425TCTTTCACGAACACAAACCCA2918SFTNTNP4161119.24426TCGAACGCTGGCTACCACTCG2919SNAGYHS4162119.169427GACTACAAAAACAGCGCGCCA2920DYKNSAP4163119.136428GTCGGGAAAAACTCGTACGAA2921VGKNSYE4164119.129429GCTTACGCAGGTGTACTTGGG2922AYAGVLG4165119.123430ACGACGTCTGAGCGTGTGAAT2923TTSERVN4166119.105431GACACCGGAATCAAAAACGTT2924DTGIKNV4167119.05432TCGACCAGCTCTCTGGTTCCC2925STSSLVP4168119.006433TGGAGCGCCGGCGAACGGGTG2926WSAGERV4169118.995434AGTTCGGGGAGTTTGATTACT2927SSGSLIT4170118.945435TGGATTTCTACTGAGATGAGG2928WISTEMR4171118.93436TTTGCGGCTGGGGCGCATGGT2929FAAGAHG4172118.92437ATAGGCGACCGCGACCAACGT2930IGDRDQR4173118.886438AGTACGATTGGTAATTCTACT2931STIGNST4174118.8619439GGAAGTGGCACCGTCGGTCGA2932GSGTVGR4175118.714440CATGTTACGGCGGTGGTTGAT2933HVTAVVD4176118.706441GATAAGGCGGGGGTGGCTAAT2934DKAGVAN4177118.67442CGTCTGACTGATACTATGCAT2935RLTDTMH4178118.589443CTGAACACTCTAATCCACAAA2936LNTLIHK4179118.565444AGTTATCAGAATCCTCCGCCT2937SYQNPPP4180118.512445TTGACAGGATTAAACGCTTTC2938LTGLNAF4181118.45446AGTCCTGTGCTTTCTCCTTCG2939SPVLSPS4182118.377447GTTCAAACACACATAGGAGTC2940VQTHIGV4183118.36448CATATGTCTTCTGTTGCGACT2941HMSSVAT4184118.34449GGAAAAGCCAACGACGGTTCT2942GKANDGS4185118.333450AGTACTAACGACGAACGCAAA2943STNDERK4186118.28451CAGGGGGGGAATAGTCGGTTT2944QGGNSRF4187118.236452CCTAACAACGAAAAAAACCCG2945PNNEKNP4188118.22453GTGGCTGCGACGGGTGGTACT2946VAATGGT4189118.173454GCGATTGTGGATAGGGGGAGT2947AIVDRGS4190118.167455TCCCAACACCACACGCCACTG2948SQHHTPL4191118.137456TTACAAAGCTCGATGAACGTA2949LQSSMNV4192118.073457CGAGAAACCAACCCGTCTGAA2950RETNPSE4193117.941458GGGTTCGGGCACCTGCCCGAA2951GFGHLPE4194117.86459CGGAATGCTACTGTGACTGTT2952RNATVTV4195117.852460GTTTCAAACGCTTCGGGCTTA2953VSNASGL4196117.707461GATCGTCCGAATAATGAGTCG2954DRPNNES4197117.7462CAGGTTAGTCTGGTGAAGTTG2955QVSLVKL4198117.643463AGTAATATGCGTGAGGAGATT2956SNMREEI4199117.629464GATATTGGGCGTTCGAATAGT2957DIGRSNS4200117.45465GATCATATGAATTTGAGGTCT2958DHMNLRS4201117.365466ATTGAGCGTAGTAGTGATCGT2959IERSSDR4202117.358467TTGTCTCAGAATTTTAATCCT2960LSQNFNP4203117.3026468TATTCTATGGGTCAGCAGCCG2961YSMGQQP4204117.283469TACACACAAGGGATAATGAAC2962YTQGIMN4205117.22470ATGCTGTCTCATGGTGCGCTT2963MLSHGAL4206117.165471GCTTATAATGCTCGTCTGCCT2964AYNARLP4207116.957472AGACACTACTCCGACAACGCC2965RHYSDNA4208116.945473GCACACACAGCCATGACCTAC2966AHTAMTY4209116.935474CTAACAGGCTCTGACATGAAA2967LTGSDMK4210116.89475ACCTTACACACGAAAGACTTG2968TLHTKDL4211116.879476TCGGGTCAAAACGGTACATCA2969SGQNGTS4212116.851477CGTGGGGACGTCCACACCAAC2970RGDVHTN4213116.829478ACCGGAACGGCTACACTCCCA2971TGTATLP4214116.72479CTGGGTACGCTGCTTAGTCAG2972LGTLLSQ4215116.72480GTCCTCTCCTCCAACCTGTAC2973VLSSNLY4216116.707481AGTTTGGGGTCGGATCGTATG2974SLGSDRM4217116.61482AGGGGAGATCTTTCTACGCCT2975RGDLSTP4218116.59483AGGATGTCGGAGAGTTCTGAT2976RMSESSD4219116.585484ATGACTGAGAAGGCTTCTATT2977MTEKASI4220116.54485ACAGAACAATCTTACTAACGA2978TEQSY*R4221116.54486GTTGAATCTAAATCCGAACCA2979VESKSEP4222116.536487ATGAATCTTGTGAGGGATTCG2980MNLVRDS4223116.526488CAAAACCACTCTATAACAACA2981QNHSITT4224116.51489ACGCTGGACAACAACCACAGC2982TLDNNHS4225116.42490ACGAAGAGTTTTAATGATCTT2983TKSFNDL4226116.38491GCCACAGAACACTCAGGGCGC2984ATEHSGR4227116.34492CAAGGGACTCTCTTGTCTCCA2985QGTLLSP4228116.293493ACATTCCACCAAGGGGTCAAA2986TFHQGVK4229116.175494TGTCAGCGGGCTGATTGTGCG2987CQRADCA4230116.17495CGGTATGATGGTACTCTTAAT2988RYDGTLN4231115.929496CAAGGCGGTACAAACAACCCC2989QGGTNNP4232115.853497GGGGGTAACTACCACACCACT2990GGNYHTT4233115.838498CTGGTTGTTCAGAGTGCGCAG2991LVVQSAQ4234115.7942499TATCCTCATGAGAGTAAGAAT2992YPHESKN4235115.731500GAGATTGTTAGGCATACGCAT2993EIVRHTH4236115.724501GACCGGACAAACAACATGAGC2994DRTNNMS4237115.705502TCCGTAACCAACGGAGCGGAA2995SVTNGAE4238115.66503AGCGGACAAAAAAACTCAGAA2996SGQKNSE4239115.653504GAGCAGAAGAAGACTGATCAT2997EQKKTDH4240115.565505AATATTAATGGTGGGGGGAAT2998NINGGGN4241115.563506AAGCTGCATACTAAGGATCTT2999KLHTKDL4242115.54507AGCTTCTTGGTAGCCCACCCA3000SFLVAHP4243115.4508TACCAACAAAACATAGAAATC3001YQQNIEI4244115.388509AGGGGTGATCTTTCTACGACT3002RGDLSTT4245115.31510GCGAACCTCAACTTGACCAGT3003ANLNLTS4246115.305511ACGGTGCAGCATGCGGCGACG3004TVQHAAT4247115.231512ACCGTAAACCTCCTAGCGGCA3005TVNLLAA4248115.223513AACCAAAGAGTTGAACAAAAA3006NQRVEQK4249115.222514AATACTTATACTGCTGCGAAG3007NTYTAAK4250115.189515ATCCAAAGAGACGTGGGCCAC3008IQRDVGH4251115.098516ATCTCAGAAATGACTAGGTAC3009ISEMTRY4252115.098517ATTGCTACTAATGTGATTTAT3010IATNVIY4253115.089518AACGGCAACCACTCCATAGAC3011NGNHSID4254115.062519ACGAGTATTGGTAGTGCTAAG3012TSIGSAK4255115.036520AACGTACACTCTGTTGACAAA3013NVHSVDK4256114.987521GAACTCTCCGTTCCGAAACCA3014ELSVPKP4257114.93522TTCCTCGACAAATACAACTAC3015FLDKYNY4258114.888523TACATCCCGAACAACTCAGGA3016YIPNNSG4259114.881524GGGCTAGGACAACCCCAACTC3017GLGQPQL4260114.817525GAGGGGAGTCAGGGGAATCAT3018EGSQGNH4261114.66526AATATTTATATGGCGAGTGGT3019NIYMASG4262114.66527AATTTGCAGACTGGTGTTCAG3020NLQTGVQ4263114.65528ACCGTCGCTCCCTACAGTAGC3021TVAPYSS4264114.65529TCAAACTACTCTGACGGAATA3022SNYSDGI4265114.649530GCTACTTACGTTGTCGGAACA3023ATYVVGT4266114.64531TCAAGGGAAGCGGGTTCAACT3024SREAGST4267114.622532GCCGGAAAAACCCACGCCGAC3025AGKTHAD4268114.6533CCGCTTTCTCTTCATAATAGT3026PLSLHNS4269114.589534CTTCGAGACCTAAACGGAGGA3027LRDLNGG4270114.553535GATAGGACGTATTCGAATACG3028DRTYSNT4271114.548536TCGGTCACCAGTGGAACACAA3029SVTSGTQ4272114.541537AATATGACTTCGGCTTATCAT3030NMTSAYH4273114.52538GTTATGGGTGGTCCTGGGATT3031VMGGPGI4274114.491539GCTGGGACTCATACTGATAAG3032AGTHTDK4275114.444540GGTACTATGAATATTGGTATT3033GTMNIGI4276114.356541ACAGCCGGCGGCGAACGCGCC3034TAGGERA4277114.34542GGTATGACTTCTAATCAGGTT3035GMTSNQV4278114.298543CATTTTTCGCAGATTACTAAT3036HFSQITN4279114.278544AGCAGGATAGAAAACAACAAC3037SRIENNN4280114.055545GATACGGCGAGTTATAATAAT3038DTASYNN4281114546GTGAATCAGAGTCCTGGGGCT3039VNQSPGA4282113.85547AATAATATGGGTCATGGTCAT3040NNMGHGH4283113.837548TCGCGGCTATCACAAGACCCC3041SRLSQDP4284113.832549TCTACGTCTCAGGCTGTGCAG3042STSQAVQ4285113.802550CGATGGCAAGGACTGAGCGCG3043RWQGLSA4286113.76551GCGCATATGCATTCGGAGTTG3044AHMHSEL4287113.74552AATAATCTTACGAATTCGACG3045NNLTNST4288113.736553CAGCCTAGTGCGAGTGAGCTT3046QPSASEL4289113.731554GGGACTTCCTTGGAAAACCGA3047GTSLENR4290113.709555CTGTCTAATTCGATTACGCCT3048LSNSITP4291113.683556ACCATAGTGTCCACTTCTTAC3049TIVSTSY4292113.628557ACCCTAGGCTACCCAGACAAA3050TLGYPDK4293113.563558TCAAGACACGACGTCCGAAAC3051SRHDVRN4294113.559559AATGGTAGTGTGGCTAATCCT3052NGSVANP4295113.48560GCGATGGATGGGTATAGGGTT3053AMDGYRV4296113.462561TGGACGGGCGCACAACCTTCT3054WTGAQPS4297113.3493562AAAAACGGCGCCATAGGAACA3055KNGAIGT4298113.335563GTACTTCCAAGTCGGATCGCG3056VLPSRIA4299113.3564GATAATGTGAATTCTCAGCCT3057DNVNSQP4300113.207565GGCGTAAACGCTAGCTACAGC3058GVNASYS4301113.174566CTGTCTCACGCCATGGACCGG3059LSHAMDR4302113.127567AGGGCTCATGGGGATAATCAG3060RAHGDNQ4303113.036568TTGCAGACGCCTGGGACGACG3061LQTPGTT4304113.01569ACTCAGGTTGTTAGTATTTAT3062TQVVSIY4305113.001570CAGGTTCAGGGGACTCTGGGG3063QVQGTLG4306112.9928571GTGGGCAACCAAAACTTACCC3064VGNQNLP4307112.889572TATGTTGATTATAGTAAGTCG3065YVDYSKS4308112.872573CTGCTTAATTCTTCGGGTGTG3066LLNSSGV4309112.857574AATCAGTCGCTTACTATGGAT3067NQSLTMD4310112.793575GCTGGTAAGGATCTTAGTAAT3068AGKDLSN4311112.792576TCTTACGTTAGCGTCCCCGCC3069SYVSVPA4312112.668577AATGAGGGGCGTGTGCAGACT3070NEGRVQT4313112.6219578ACTTTGACGCAGACTGGGATG3071TLTQTGM4314112.588579GGCTTCGCATTAACTGGCACC3072GFALTGT4315112.564580CAGTCGACGCTGAATAGGCCT3073QSTLNRP4316112.5575581ACAACAACACACTCCATCTCC3074TTTHSIS4317112.547582AACACACACAGACAAGAATAC3075NTHRQEY4318112.522583TCCCAAATAGTCAACACCACA3076SQIVNTT4319112.519584CTGGTGCTTGAGATGCAGACG3077LVLEMQT4320112.492585AACGACATCTCCACCCAACGG3078NDISTQR4321112.444586TACACCGCCGACAAAAAACAA3079YTADKKQ4322112.402587TTCGGAGCAACCACCACAGCA3080FGATTTA4323112.399588GTTCAGATTTCTATGAATAAT3081VQISMNN4324112.364589ATGCATGCGCAGGAGTCTCGT3082MHAQESR4325112.324590CATGTGAATACTGCTGATCGG3083HVNTADR4326112.313591TACAGTACAGACTCCACCAAA3084YSTDSTK4327112.271592GGACACGACCGAACACCAAAC3085GHDRTPN4328112.213593ACGAGTGGTGTGCTTACGCGG3086TSGVLTR4329112.212594AATATTGCTATGTCTAAGATT3087NIAMSKI4330112.204595ATGGGGACTGAGTATCGTATG3088MGTEYRM4331112.185596CCTTATGCGAATAGGCTTGAG3089PYANRLE4332112.174597CCGCTTCAGAATAATAAGACG3090PLQNNKT4333112.172598TCCTTGACGGAAAAAGCGCCG3091SLTEKAP4334112.15599AATATGGTGTATACGAATGTG3092NMVYTNV4335112.077600ATGTTAAGTGCCACCCAAGGG3093MLSATQG4336112.047601AACATGACTCACTCAACCGTA3094NMTHSTV4337112.0108602ATTTATACGAATAGTCATGTT3095IYTNSHV4338111.93603TGGTCGCATGATCGGCCTACT3096WSHDRPT4339111.926604GAAAAAGGCACACCAAGTAGC3097EKGTPSS4340111.922605CATCATTCTACTGAGTCGTTG3098HHSTESL4341111.911606CCAAAAAGCACCCAAGTAATG3099PKSTQVM4342111.846607AGTGATAGGACTGCTCAGCAG3100SDRTAQQ4343111.845608GCTACCCTCGCACGGACCTCA3101ATLARTS4344111.8417609ATTTCTCAGGTGTCTTTTAAT3102ISQVSFN4345111.81610CATTATGGGAATAAGGATATT3103HYGNKDI4346111.805611AATGATGGGACTGATCGTAGG3104NDGTDRR4347111.574612ACCAACCACATAACCGGTCCA3105TNHITGP4348111.551613ACTAATTCTAATCAGAGTTCG3106TNSNQSS4349111.532614GTGGCGACTCATTATAATGAG3107VATHYNE4350111.52615GACCTCGGTACGGCTAGAACC3108DLGTART4351111.516616GCTCTTAGTCAGAGTGCGGGT3109ALSQSAG4352111.4957617AAAACCACCCTACACCAAGCA3110KTTLHQA4353111.46618ATGATAAACGCCATAACTCCA3111MINAITP4354111.432619GGGTCTACGCCGGGGGCGAGT3112GSTPGAS4355111.327620AATGAGAAGCCGCAGTCGACG3113NEKPQST4356111.309621TCATTGATGGGCAGTGCAGGA3114SLMGSAG4357111.287622ACCGACACGCTCAGCGAAAGA3115TDTLSER4358111.25623GCCTCGCAATCAGAAAAAAAC3116ASQSEKN4359111.223624GCTGTTAGAACACCGGCAATG3117AVRTPAM4360111.215625CCTAATGCTAGTTTTGGTCCG3118PNASFGP4361111.172626AAAGCCCACGTTGTAGAAATA3119KAHVVEI4362111.166627TATATTTCGGCGCCTCCGATG3120YISAPPM4363111.15628CCAATCCAAAACGAATCGTCC3121PIQNESS4364111.128629GGCGTAACCAACGCTTCCAAA3122GVTNASK4365111.107630GTAAACGGGGGAAAACCAGTC3123VNGGKPV4366111.096631AGTGTTCTGAGTAGTTCGACT3124SVLSSST4367111.07632TTAGCACAAGGCACGGACCGG3125LAQGTDR4368111.032633CAGTCTGTGTCGACTGGGGCG3126QSVSTGA4369110.982634TTGACGCAGGTTTATCATGAG3127LTQVYHE4370110.91635AGAGAAATGAGCAGCCTATCT3128REMSSLS4371110.891636ACGAGTACGATGACTGCGCGT3129TSTMTAR4372110.835637ACTATTCAGCAGGTTAGTAAT3130TIQQVSN4373110.832638AGGACGCAAGCAGGGGACTCA3131RTQAGDS4374110.83639AATACTTATACTGCTGGGAAG3132NTYTAGK4375110.816640AATGAGCAGAATACGCCGAGT3133NEQNTPS4376110.79641GGATTCGCCCAACAAGAAGCG3134GFAQQEA4377110.775642AGTCCGCAGCATGGTGTTATT3135SPQHGVI4378110.7643GCAGTCCACGCAACATCATCA3136AVHATSS4379110.653644GGAGACACCCGTGGTGCACAC3137GDTRGAH4380110.63645GTAAGAGAAACCACACACCTC3138VRETTHL4381110.627646CTTTCTCAACAACGCGACTAC3139LSQQRDY4382110.6647GCGACTAGGGGTGAGTCGTCT3140ATRGESS4383110.56648ACTAATGATTCTGTGGGTAGT3141TNDSVGS4384110.545649CTTACTAATAATTTTAAGGAT3142LTNNFKD4385110.519650GTGAATGGGACTCAGATTTTT3143VNGTQIF4386110.47651GGTAATACTGGGAGTCCGGGG3144GNTGSPG4387110.431652TGGACAGCTAACCAAGGCTTA3145WTANQGL4388110.43653AATACTACTCCGACGAATCAT3146NTTPTNH4389110.42654GAACGAGTCAACGGGATGGCA3147ERVNGMA4390110.405655AAAGTCACAAACAACGCATAC3148KVTNNAY4391110.363656TTATCCTCCGAATCACCCAGG3149LSSESPR4392110.346657CATACGGCGGCGGTTGCTACT3150HTAAVAT4393110.27658TACGACAGCCGACTCTACGCG3151YDSRLYA4394110.263659ATAGAACACATGCTTAGACCC3152IEHMLRP4395110.221660TACCTAGAATCCAACTACACC3153YLESNYT4396110.18661GCGTACTCATCTACCGGGCAC3154AYSSTGH4397110.176662ATCGACATATCGACGCAAAGC3155IDISTQS4398110.14663ACAACAAACTCAGGCGCGACG3156TTNSGAT4399110.139664AACGTGCTAACCACGGTTGTC3157NVLTTVV4400110.107665ACAACCGGAATCGAACGTTCC3158TTGIERS4401110.106666GCACGAGTGGACACCAACCAA3159ARVDTNQ4402110.09667CAGAGTGTGAAGGAGGCGATT3160QSVKEAI4403110.069668GCGTTGCTTAGTGTGAATGAG3161ALLSVNE4404110.013669GGGCGTGATAATCATCATGCG3162GRDNHHA4405109.959670ATTCAGTCGCAGTCGCAGTTG3163IQSQSQL4406109.941671AGTGAGGGTAGTTCGCGGTCG3164SEGSSRS4407109.9403672GACGTCCAAAACATACGCGAA3165DVQNIRE4408109.921673AAAGGCCACGCCTACGAAGCC3166KGHAYEA4409109.897674TATGTTAGGGCGCAGGATCAG3167YVRAQDQ4410109.876675GTCGACGAATACCGAAGCCGC3168VDEYRSR4411109.853676ACTCTCTCAGGCTACATGAGA3169TLSGYMR4412109.808677CCTAGTGTCCGTTTGCCCTTA3170PSVRLPL4413109.742678AACATAGCAGGCGGAGAACAA3171NIAGGEQ4414109.702679CTGCTCCAATCGACCTACTTG3172LLQSTYL4415109.672680CAGTCGGATACGACTTCGATT3173QSDTTSI4416109.605681ATTAGGTCTGGGAATGCGATG3174IRSGNAM4417109.554682ATGCTGTCTCAAGTCTTAACA3175MLSQVLT4418109.536683ACAGAACGCCAAATCGAATTA3176TERQIEL4419109.488684GGAACCCACGCCTCAGCATAC3177GTHASAY4420109.477685GTTGAGTCTTCTTATTCTCGG3178VESSYSR4421109.457686GGTGGGAATTATCATACTAAG3179GGNYHTK4422109.445687CCCACCAGTCACCAAGAACCC3180PTSHQEP4423109.418688ACCATAATCGGTGTCTTACCC3181TIIGVLP4424109.381689TCTAACAGCGGTTCTACCCTC3182SNSGSTL4425109.379690TCGATAACGACCGTAGCGAAC3183SITTVAN4426109.347691GCGTCTCCGGCGCAGACCGGC3184ASPAQTG4427109.331692TCGTTGCCGAGTCATAGTAAT3185SLPSHSN4428109.3106693CTACACAACGCCGTCGGACCC3186LHNAVGP4429109.307694CAAGCCCCGCCAACAGCACAA3187QAPPTAQ4430109.294695CCTAATACTGCTAGTAATTTT3188PNTASNF4431109.249696CCCTCCAACAGTGAAAGATTC3189PSNSERF4432109.227697GAACTCCACGCACAACAACCA3190ELHAQQP4433109.194698GGTTCTTATTCTGATGGTAGT3191GSYSDGS4434109.162699TATGGTGTGCAGGCGAATAGT3192YGVQANS4435109.152700GAAGTAGGTAAAACCACCCAC3193EVGKTTH4436109.116701ACTTCGCAGGGTAGGAGTCCT3194TSQGRSP4437109.097702GTAGAACACGTAGCCCACCAA3195VEHVAHQ4438109.092703ATCCAAAGCAGCTACAACCGC3196IQSSYNR4439109.073704ACGCTATCGGTTACCCTGGGT3197TLSVTLG4440109.046705CGGAATGAGCCGGTTAGTACT3198RNEPVST4441108.981706GTGATTGTGGGGAGTAATGAG3199VIVGSNE4442108.955707GAGCTGTCTACTCCTATGGTT3200ELSTPMV4443108.948708GCTTACAACGACCTACGATCA3201AYNDLRS4444108.942709AACGCGAACTCCGGTGAACGA3202NANSGER4445108.906710TTGTCATCACAATGGACACAA3203LSSQWTQ4446108.9711ATCAACGCCGGCAACTACCGA3204INAGNYR4447108.883712CTGAGGTCGAGTGAGGCTCCG3205LRSSEAP4448108.866713ACGTCTGATACGAATGCTAGG3206TSDTNAR4449108.858714CCGAATTCTCCGCATGGTTCT3207PNSPHGS4450108.84715ACCCAACACCTACCATCCACA3208TQHLPST4451108.803716GTGCATGGGAATGCTCCGGCT3209VHGNAPA4452108.783717TCTTCTCAGCGTGATTCTGTT3210SSQRDSV4453108.754718CCCCCCTCAGTTGACCGAAAA3211PPSVDRK4454108.751719GAGACTCTGCCGTATAAGAGT3212ETLPYKS4455108.728720CATCTTAGTCAGGCTAATCAT3213HLSQANH4456108.727721AAACCGCTAAACGGTACCAAC3214KPLNGTN4457108.683722TGGCAAACCAACGGCATGCAA3215WQTNGMQ4458108.68723ACCGTGAACGTCCACTCCGAC3216TVNVHSD4459108.659724ACCCAATACGTCGTTGCCCCT3217TQYVVAP4460108.64725AACGTCGACTCCTCTAACGTG3218NVDSSNV4461108.62726AACGGATACCAACTACAAATC3219NGYQLQI4462108.573727GAAGAAACACGGACCAGAATG3220EETRTRM4463108.571728ACCTCTCCAGCCTCTGACCGG3221TSPASDR4464108.552729CATAGTGGTGCTGGGGTTCTG3222HSGAGVL4465108.539730GCTGCTAATCCTAGTACGGAG3223AANPSTE4466108.527731ATGTTGGTACAAAACACACCC3224MLVQNTP4467108.482732GTGCAGCAGAATAATATTAAT3225VQQNNIN4468108.473733CATGATGGTTATGTTCCTAAT3226HDGYVPN4469108.469734AACTCAGGTAACAACCCCATC3227NSGNNPI4470108.467735ACGGACAACCCGTCCTACAAA3228TDNPSYK4471108.453736GGAGGCTTAAGTTTATCCTCG3229GGLSLSS4472108.431737AATAATGAGAATACGCGTAAT3230NNENTRN4473108.418738AAGAATAATAATTCTGATTCT3231KNNNSDS4474108.367739AAGGATGAGCATCTTCATTAT3232KDEHLHY4475108.358740AATTTTACTATTACGGAGGCG3233NFTITEA4476108.32741TTGAACCAAAACAGTGTCTCC3234LNQNSVS4477108.304742AATTCTCATGTTCCTAATAAT3235NSHVPNN4478108.289743AATTCTACGCATATTAATTCG3236NSTHINS4479108.2563744CATATGTCTAGTTATTCGTCG3237HMSSYSS4480108.253745AACGTACCCAACGGACAAGGA3238NVPNGQG4481108.25746AACGGTCCGACCGGATCCGCC3239NGPTGSA4482108.245747AAAAGCAACGCGGGATTCGGT3240KSNAGFG4483108.23748GCGGCCGCACTAGAAACAATA3241AAALETI4484108.223749AACCGTCAAAGGGACTTCGAA3242NRQRDFE4485108.196750GGGTCAGGGAACGAACCCGGG3243GSGNEPG4486108.192751GTTAGTGTGGCTGTGCCTGCG3244VSVAVPA4487108.11752CACTCTAACACACACTACGAA3245HSNTHYE4488108.11753CCTGACAGAGCGAACGACAAA3246PDRANDK4489108.058754CAAGTTGGGGCTCTAATGGTT3247QVGALMV4490108.037755TTAACACCCCAAGGGACTAGT3248LTPQGTS4491108.028756CTATACGACGGAAAACACGTC3249LYDGKHV4492107.972757CTAACCGAATCTGTGAGAAAC3250LTESVRN4493107.93758AGTACTTATGGGAATACTTAT3251STYGNTY4494107.929759AATGCTATTTCTACTAATAAT3252NAISTNN4495107.907760ATTGCTCATGTGTCTACTAAT3253IAHVSTN4496107.849761AGTGAGGAGAGGACGCGTGCG3254SEERTRA4497107.833762CGTTGGTCTGAAAACAACTCC3255RWSENNS4498107.83763GATGGTAATAATACGACTTAT3256DGNNTTY4499107.748764GTGACGACTGTTGATAGTGCT3257VTTVDSA4500107.738765ACCGTAAAACAAACAAGTCCG3258TVKQTSP4501107.7213766TCTATCTACCTCGCGTCCACT3259SIYLAST4502107.712767ACGACCCGAAACGAACACTCG3260TTRNEHS4503107.707768TCGTATGATATGCATACGAAT3261SYDMHTN4504107.705769GTCTCTACATACCTCCTGGCA3262VSTYLLA4505107.687770GGAGAACAAAGCCACAACCAA3263GEQSHNQ4506107.684771ACTGCCAACAACCACTCTCCG3264TANNHSP4507107.671772CAATTCCACGGGACATCTGAA3265QFHGTSE4508107.652773AACGTTCTGGGAGCGTCTAGC3266NVLGASS4509107.64774AGGGATAGTACTATTAGTCGG3267RDSTISR4510107.635775GTTATTGGGACTTCTAGGGAT3268VIGTSRD4511107.5934776AATTATGAGAAGGAGTTTGTT3269NYEKEFV4512107.592777ATGGACCAAAGCCACTCCCGA3270MDQSHSR4513107.563778AATTCTCAGAATCCTCAGGGT3271NSQNPQG4514107.562779CACACGGGCACGGACAACCGA3272HTGTDNR4515107.5323780TATAATACTGTTGATCAGCGG3273YNTVDQR4516107.523781AAAGAAAGCCTCGAAGACGTC3274KESLEDV4517107.49782ACTGCGAATAGTACGTATGTG3275TANSTYV4518107.479783TATCTGAATAGTACGCAGATT3276YLNSTQI4519107.436784CGTGTTGAAGACACCAACTCC3277RVEDTNS4520107.416785AACGACGCACGCAACCGTGCA3278NDARNRA4521107.37786AATACTAATAATCAGGAGCAG3279NTNNQEQ4522107.332787ACCGTCGGATCGAACAGTATA3280TVGSNSI4523107.3788TATGGGGAGCGTGCTAGGACG3281YGERART4524107.297789CCGACCGGAGGCTCACCACCA3282PTGGSPP4525107.265790CTTGGGCAGGTTAATTCTACG3283LGQVNST4526107.229791GTCTCGGGTCCGGTATCGGTC3284VSGPVSV4527107.222792GGTACTAATCATGATTTTTCG3285GTNHDFS4528107.169793AAGACGCTTGATAATAATGCT3286KTLDNNA4529107.165794CACAGTGAACTACGTCAAAAC3287HSELRQN4530107.157795GAGAAGAATCTGACTAATGCT3288EKNLTNA4531107.131796ACCGGACTCGGAGGCAACAGT3289TGLGGNS4532107.113797AAAGACCACATCCTCAGCCTC3290KDHILSL4533107.108798ATAACTACTGGCGGAGTGCTA3291ITTGGVL4534107.108799CTGGCTGATTCGAATTCTAAG3292LADSNSK4535107.1800AGTATTTCTGATAAGAATCAG3293SISDKNQ4536107.08801TATATTGCTGGGGGGGAGCAG3294YIAGGEQ4537107.069802TTGCCGGATAAGGGGCGGATT3295LPDKGRI4538107.06803TTGATCCAAACGCAAGGCACG3296LIQTQGT4539107.042804TACTCCGGAGAACTAAACAAA3297YSGELNK4540107.037805TGCGCATCAGAAGTTTGCCAA3298CASEVCQ4541107.035806CTTATGGCTGCTAATACTGCG3299LMAANTA4542107.032807CATCAGTCTTTTGATGCTGGT3300HQSFDAG4543107.001808GGGGAGACGCTGAGGTCTCAG3301GETLRSQ4544106.999809CAGACTGATGGTCCTAATTTT3302QTDGPNF4545106.978810ACGACGACTAATGTGAATTTT3303TTTNVNF4546106.969811AACATGACCAACGAAAACGGA3304NMTNENG4547106.938812GGGTATAGTCCTTCGACGCCG3305GYSPSTP4548106.892813TTGCAGGTTACGGTTCATAAT3306LQVTVHN4549106.879814GATCTGACGCATGTTCATCGT3307DLTHVHR4550106.874815ACGGAGCTTAGTGAGTATACT3308TELSEYT4551106.852816ATGACAGTCGCCAGTACTAGC3309MTVASTS4552106.843817AGCAGTCAAGCCCACGGCCCA3310SSQAHGP4553106.822818ACCAGAAGCCCGAACGAAGAC3311TRSPNED4554106.81819GATAATAATAAGCATGGTACT3312DNNKHGT4555106.806820AGGGAGATTGTTCATAGTAAT3313REIVHSN4556106.802821CGGAAACTTGAACTCGACCTA3314RKLELDL4557106.801822ATCTACGAAACCGTAACCTTG3315IYETVTL4558106.801823AATAGTGGTAGTACGAGTTTT3316NSGSTSF4559106.783824CCAAGTACGAACGAAAGCCGC3317PSTNESR4560106.782825CAAGCCGACCTCAGGTACAAA3318QADLRYK4561106.773826GATCAGCCGGGGTATGTGCGT3319DQPGYVR4562106.7387827GATGCTATGCTTGCTCATCCG3320DAMLAHP4563106.735828ACACGTCACGACGGCAGTACG3321TRHDGST4564106.675829CTGGCGAATATGAGTGCGCCG3322LANMSAP4565106.664830ACTGGTCATCCGCCGGCGGCG3323TGHPPAA4566106.654831TCGAGTATTAGTCTGCGGTAT3324SSISLRY4567106.645832ATGCACGTCGACAAAACGAGT3325MHVDKTS4568106.639833GGGAGTGATTCTAAGCATCCT3326GSDSKHP4569106.5782834GGAGAAAGCTCCTCAATAAGC3327GESSSIS4570106.551835GTCGTCCACTCACACAGTGAA3328VVHSHSE4571106.496836AGTGTGCGGGCGCATGTTTTG3329SVRAHVL4572106.487837GCGGATGGGGCTAAGTCTGCT3330ADGAKSA4573106.485838GGGGAAGCACGCCGAGAAGCC3331GEARREA4574106.442839TTTAATGCTACGGTGGTGCAT3332FNATVVH4575106.437840TGGACGGAAGGGGGCTCAGGA3333WTEGGSG4576106.423841GATTCTTCTTATACGCATCCG3334DSSYTHP4577106.422842TTCCCAAGTAGGGACAACGTA3335FPSRDNV4578106.39843GCCATCACGCACATCGGTACA3336AITHIGT4579106.365844GCTTTTAAGTCGGGTAGTATT3337AFKSGSI4580106.334845ATGTCAAACGCCTCCTACATA3338MSNASYI4581106.319846GCGGAGAGGAATGATAGGACG3339AERNDRT4582106.305847ACATTAGAAACAACCCGCAGC3340TLETTRS4583106.244848CGCTTACACGGCTCAGACTCG3341RLHGSDS4584106.237849TATGAGGGGCATATGAATACT3342YEGHMNT4585106.2354850TCTGTGACGACTAATCTGATG3343SVTTNLM4586106.217851TTGCGTGATCAGACTAGTATG3344LRDQTSM4587106.167852CCCGCCAGTCACAGCGCGGGA3345PASHSAG4588106.151853GTGGTTGAGAATTTGAGGCAG3346VVENLRQ4589106.147854CAACAATCACAAAACTCTATA3347QQSQNSI4590106.115855CTTGTTGATACGGATAGGAAT3348LVDTDRN4591106.108856AACGAAATGGGAAACTACGTC3349NEMGNYV4592106.104857TCCACCGACCCCCGATACTCA3350STDPRYS4593106.097858ACTAATGGTATTTATCAGCCT3351TNGIYQP4594106.095859TGGGTAAACAGTGTGGGCAAC3352WVNSVGN4595106.084860GGGGTATCTAACAACTCTAGC3353GVSNNSS4596106.079861AATGTTAATGCGCAGAGTAGG3354NVNAQSR4597106.064862ACGACGCCGCCTTTTTCTAAT3355TTPPFSN4598106.044863ACAGGCAGCTCCCACACCAAC3356TGSSHTN4599106.0345864TACGTCGACAAATCAATGACA3357YVDKSMT4600106.009865CTAATCAAAAACAACATGCTC3358LIKNNML4601105.9827866GGGGGTACGGGGTTGTCGAAG3359GGTGLSK4602105.98867GCTCTTCATAATCTGATGAAT3360ALHNLMN4603105.977868GTGCATGTGACTAATGTGTTG3361VHVTNVL4604105.924869TCGACGACGCACCCTTCCGAA3362STTHPSE4605105.898870AGCGTAGGTAGTCCAACACAC3363SVGSPTH4606105.8936871ATGAGTAATGATTTGCCTGGG3364MSNDLPG4607105.877872TTCTCGTCAACCGAAGCCAGA3365FSSTEAR4608105.858873GCCGGTCACCAACAACTGGCC3366AGHQQLA4609105.846874GGTACCATATTACCAAACCAA3367GTILPNQ4610105.829875AGCGCGGTTTCTGGTAGCAGC3368SAVSGSS4611105.825876GAGGTGTCTAGGGATGGTCTG3369EVSRDGL4612105.814877CAATCACTCAAAGACGGCACT3370QSLKDGT4613105.804878ACGCGTGAGGGTAATCATGCT3371TREGNHA4614105.8879GTGGCGACCCAAAACCTTCTT3372VATQNLL4615105.795880GCCGAAATGACGCACCGCCTC3373AEMTHRL4616105.771881CAACGGCCAGACCCGCTTAAA3374QRPDPLK4617105.764882GAACACATCTCTAGCTACGGA3375EHISSYG4618105.752883CAAAAAAGCAACGACCAAAAC3376QKSNDQN4619105.744884AATCTTGTGATGAGTGGGACG3377NLVMSGT4620105.742885GGAGCGGGACAATCTCACGTG3378GAGQSHV4621105.721886CTCAACCACACAATGCCCCTC3379LNHTMPL4622105.713887GTATCACAATCACACGACGTG3380VSQSHDV4623105.687888GCTAATTCTGCTACTAATCAG3381ANSATNQ4624105.679889GGCACAGGAGGTAACCGAGAA3382GTGGNRE4625105.671890GCGAAGTCGTCGATTATTTTG3383AKSSIIL4626105.661891GGAGGAACAGCCCTTGGGAGC3384GGTALGS4627105.613892AACAAAGTAGAATCTGACCCA3385NKVESDP4628105.59893AACTCGAAACAACCCGACGTC3386NSKQPDV4629105.572894AGTTATGCTGATCGTCGGCTG3387SYADRRL4630105.567895AATGTGAATCCGAATGGGCCG3388NVNPNGP4631105.53896GAACACAACTCAAAAACTTAC3389EHNSKTY4632105.496897ACCCAAGGATCTAACACCACA3390TQGSNTT4633105.489898AGCAACGTATCAGCTTACGCA3391SNVSAYA4634105.48899GCGTACAGTGACAGCGCCCGC3392AYSDSAR4635105.457900GGGTCGCAATACGCGAACCGC3393GSQYANR4636105.402901ACAATGAGCGTAACTCTGGAA3394TMSVTLE4637105.393902CAGACGACTATTCTGGCTGCT3395QTTILAA4638105.386903TTGCTCCAATCCATAGTGGTA3396LLQSIVV4639105.381904GTTCACGCTAACGCTACATTA3397VHANATL4640105.38905AACAAAACAAACGCCGACTAC3398NKTNADY4641105.38906AACTACGACACCGGCGCCAAA3399NYDTGAK4642105.378907GTCTACCACAACCGCGACGTT3400VYHNRDV4643105.358908GATTCTGCTCCGAGGTCTATT3401DSAPRSI4644105.351909TTGATTGCGAATCTGAGTAAT3402LIANLSN4645105.341910CCGCAAGACGTCCGCCAAACA3403PQDVRQT4646105.331911ACAATGACAGCAATAGCAATG3404TMTAIAM4647105.327912ACATACGCCTCTACTGAAGCG3405TYASTEA4648105.324913CCTCACGCCAACGGAGTGACA3406PHANGVT4649105.298914CGGGCTGATGTTTCTTGGTCT3407RADVSWS4650105.286915CTGACGCACATGACCGGAACC3408LTHMTGT4651105.272916GCAAACGACTCTGCCAAAACA3409ANDSAKT4652105.269917GCTAATTCTGGGTTGCATAAT3410ANSGLHN4653105.246918AACGTGGGCACCGACAGAGAC3411NVGTDRD4654105.231919GTCGGAACAACCTCGAACGGC3412VGTTSNG4655105.226920GGAGTTCTTGGGATACTGGTC3413GVLGILV4656105.184921CGAATCAACGCAGCAATCGAC3414RINAAID4657105.1475922CCCGACACTCGCCCATCCATA3415PDTRPSI4658105.135923GGTGAATCACGTACAAACATG3416GESRTNM4659105.119924ATTTTGCTTGCTCAGTCTGCT3417ILLAQSA4660105.117925TATAATAGGGATAATGGTTCT3418YNRDNGS4661105.083926TGGAATAGTCCGGGTGAGGCG3419WNSPGEA4662105.053927CTGTTGGGGGCTCATCAGCCG3420LLGAHQP4663105.052928ATTGGTAAGGATAGTGTTCCG3421IGKDSVP4664105.044929ACGCGGGAGAGTCTGGTGGAT3422TRESLVD4665105.022930GCCTCTAACCACCTACAAGCC3423ASNHLQA4666105.013931AATCTTCAGACGGGTAAGGCT3424NLQTGKA4667104.976932ACTGTAGGATCCTCATACGCT3425TVGSSYA4668104.9737933GACACTAACGGAATAAAATCA3426DTNGIKS4669104.968934AGTCTGCGGATGGAGAATAGT3427SLRMENS4670104.957935ACTAAGGGTAATAATCTGGTT3428TKGNNLV4671104.92936CATACGAATCAGATGCAGCCT3429HTNQMQP4672104.919937AACGGCAACTACGACGGCGCG3430NGNYDGA4673104.912938GAGGCGCATAATCGTGGTAAT3431EAHNRGN4674104.898939GGGACGGTTAACTCAAGTGCA3432GTVNSSA4675104.861940GGGCCGACGATGAATCATAAT3433GPTMNHN4676104.854941GTACCCAACAACAACACTTCG3434VPNNNTS4677104.834942GTTTCTAACAAATCTGGAAGT3435VSNKSGS4678104.818943TGGGGAGTCAGTAACTCAGCA3436WGVSNSA4679104.795944GTCTCTAACGTCCTCTACAGC3437VSNVLYS4680104.772945GCCGGCCAAAACAGTGTGGGC3438AGQNSVG4681104.77946GGTACGAGTCTGGAGAATAGG3439GTSLENR4682104.754947CAGATGAATATTCATGATAAG3440QMNIHDK4683104.736948CCTCAACTAAGCGGCACAGCG3441PQLSGTA4684104.733949AGTTCGACTCCGCAGGATACT3442SSTPQDT4685104.713950GTGCAGGGGCAGACCGGCTGG3443VQGQTGW4686104.688951GGTCTGACGGGTGATTTGGTT3444GLTGDLV4687104.682952AACCACCCCGCACCAAGCTCA3445NHPAPSS4688104.679953AAAGAAAAAACCACCCGCGAA3446KEKTTRE4689104.665954ACTACTAATCCGCAGACGCAG3447TTNPQTQ4690104.663955GGAGGTGAACACGCAAGAAAC3448GGEHARN4691104.66956ACGACCGAAGCTGTTGTAGCA3449TTEAVVA4692104.656957CAAAACAGTGACCTCGCCAGC3450QNSDLAS4693104.638958TACTCTACAGAAGCACGAGTC3451YSTEARV4694104.609959ACCGGACAAGCGGGCGGATCG3452TGQAGGS4695104.571960ACTTCGTCTAATCTTTATGTG3453TSSNLYV4696104.559961ACGGCTCGTGCGATTGATATG3454TARAIDM4697104.551962CAGGAGTCTAATAGGGGGGTG3455QESNRGV4698104.547963AGTATCGGATTCTCAGTAGGC3456SIGFSVG4699104.529964GAGCGGAGTACGCATAATGTT3457ERSTHNV4700104.513965GCAAACCACGACAACATCGTG3458ANHDNIV4701104.501966TGGGCTATGAATAATGTGCCG3459WAMNNVP4702104.498967TATATTGCTGCGGGTGAGCAG3460YIAAGEQ4703104.498968AGTTCGAATACTTCTGGTAGT3461SSNTSGS4704104.4928969ATGGGGAAGCATGAGGGTCTT3462MGKHEGL4705104.481970GTGCTTACTCATCTGCCGACG3463VLTHLPT4706104.4786971GAAATGGGTAACCAATACCCA3464EMGNQYP4707104.453972AGTCTGCGTCCAACCCTACCT3465SLAPTLP4708104.448973TCGGCTAACTTATACAAACAA3466SANLYKQ4709104.394974CAAAACGACAGAAAACCGGAC3467QNDRKPD4710104.391975ATTATTTCGGGTATTACGGTG3468IISGITV4711104.365976CCATCCGAAATGAGGGCCGTA3469PSEMRAV4712104.361977TTGGTTACGCAGACGCCGAAT3470LVTQTPN4713104.337978ATTGCGCAGAATGAGACGTAT3471IAQNETY4714104.336979CCATACTTAAGAAACATGGCG3472PYLRNMA4715104.321980GGCGTGAACACAAAAATCGAA3473GVNTKIE4716104.311981TACTCTTCTGAAATGAGCGAA3474YSSEMSE4717104.31982TTAGAAAACCCAACACCAGCA3475LENPTPA4718104.305983GGTGTTATGTCTAATGCTACT3476GVMSNAT4719104.289984GCCCACACTGCATTAGCGGGG3477AHTALAG4720104.27985CCTGTTGTGAGGGATCGTTCT3478PVVRDRS4721104.2336986TCTGCGGGTATGGTGAGTCTG3479SAGMVSL4722104.229987TCGGGTGTTAATAGTGAGCGT3480SGVNSER4723104.2093988AATGGGGATGTTACTAATATG3481NGDVTNM4724104.179989TCTGTTGTGCCTACGGATAAG3482SVVPTDK4725104.174990AGTAAGGGTGATCAGCTTAAT3483SKGDQLN4726104.166991GACGGAGAATCCCGATTATCA3484DGESRLS4727104.158992GGTAATATGAATCATAGTATT3485GNMNHSI4728104.15993AGTGGGCATGCTTCTCAGGGT3486SGHASQG4729104.148994GGTTGGAGTAATAATGAGTTG3487GWSNNEL4730104.145995GGTGTGCATACTCATACTGTT3488GVHTHTV4731104.139996CACGTGACAGTAACGTTAAAC3489HVTVTLN4732104.124997ACCCGTGGCAACGACATATCA3490TRGNDIS4733104.058998AGCAAAGGCGGCGACATGGTT3491SKGGDMV4734104.043999ACGCATGGTGATCATATTCAG3492THGDHIQ4735104.0321000ACTACGAATTCTCATGCGATT3493TTNSHAI4736104.0211001GTCAGAACAGTCCTTCAACAA3494VRTVLQQ4737104.0171002ACTGTGCGTTCGCCTCAGCCG3495TVRSPQP4738104.0151003AATACTTATACTGCTGGTAAG3496NTYTAGK4739104.0051004ATTAGTAATCCGGAGAATACG3497ISNPENT4740103.9981005ATCGGGTCGCCGTTGGCCAAC3498IGSPLAN4741103.9281006TATACGGGTACTCTTGTTGTT3499YTGTLVV4742103.9111007GGGCGGCACACATTAGCGGAC3500GRHTLAD4743103.9081008ACTGATGGGCCGCGTCTGGCT3501TDGPRLA4744103.8811009GGGGCAGGAAACCTGGGTACC3502GAGNLGT4745103.8731010CTGATGAATCGTAATGCTCCT3503LMNRNAP4746103.86481011AATGCTATGGCTTCTAGTAGG3504NAMASSR4747103.8261012CAGCATCGTGCGCAGGATGTG3505QHRAQDV4748103.82481013AAAATAGAAAGCGGAACCATA3506KIESGTI4749103.8221014ACTAATTATCCTGAGGCGAAT3507TNYPEAN4750103.8061015GTATACCACGGGGTAGCCAGC3508VYHGVAS4751103.8031016TCCAACGTCCACGTAGTAAAC3509SNVHVVN4752103.7911017ACATACACCGACGGGAACCCC3510TYTDGNP4753103.7881018TTTATTGCGAATACGAATCCT3511FIANTNP4754103.7871019GACGCCGGGTACGGCCACGAC3512DAGYGHD4755103.7851020GGTCTTAGTCGGAATGATGGT3513GLSRNDG4756103.7831021ATGATGGGCGCGACAACGAAA3514MMGATTK4757103.7791022CCCATCAACGTACTCACGACA3515PINVLTT4758103.7711023GCCGTAGACCAATCACGTTTG3516AVDQSRL4759103.7651024AACGCTTCTACCTACATGGAC3517NASTYMD4760103.7281025ACACAAGCAGGTCTTGCGTCA3518TQAGLAS4761103.6961026GCACAATTCGAATCAGGCCGA3519AQFESGR4762103.6931027CGGAATGGTGGTACTACGGAT3520RNGGTTD4763103.6691028GCTAATACGTATAATGTTCAG3521ANTYNVQ4764103.641029TCGGGTGTTCATAGTGAGCGT3522SGVHSER4765103.6361030AACACCGGCACCACGAGTGTC3523NTGTTSV4766103.6351031AGTACGAGTAATAGTCATATG3524STSNSHM4767103.6321032GGTGAACAACACAACGCCCCC3525GEQHNAP4768103.6291033GCTCATCATATGACGACGGAG3526AHHMTTE4769103.6141034TTGATGACTGGTACTGCGTCG3527LMTGTAS4770103.5751035GCTGCCGGAGCCGACTCTCCA3528AAGADSP4771103.5681036GTGTCTCTGAGTTCGCCTCCG3529VSLSSPP4772103.5631037CGTGTTGTAGCCGGTCCCAAC3530RVVAGPN4773103.5341038GATAAGACTGAGATGCTGCAG3531DKTEMLQ4774103.5251039GCACGAGACGACACGATACAA3532ARDDTIQ4775103.5231040TTACACCTTGGGTTATCATCT3533LHLGLSS4776103.5131041CTCGAAGGACAACGGGACGTC3534LEGQRDV4777103.5051042GCGTCGTTGTCGGCTCCGGCG3535ASLSAPA4778103.50361043AGCAACCCTGGGAACCACAAC3536SNPGNHN4779103.5021044GGGCTGAATTCTAAGGGGACT3537GLNSKGT4780103.4711045AAAACACCCTCAGCTTCAGAA3538KTPSASE4781103.471046GTGCTGGCGTCGACTGAGAAG3539VLASTEK4782103.4511047TCGGTATTGAACAAACCAACA3540SVLNKPT4783103.4411048CCCGGTAACGGACAAAGTCCG3541PGNGQSP4784103.3961049ATCTTGATGGGCGCTAGGACA3542ILMGART4785103.3851050GCACTACCATCCCACTCCTCC3543ALPSHSS4786103.3821051AGGGATCAGACTCATCCGAAT3544RDQTHPN4787103.3781052TCTGGTCCGATTCCTGCTGTT3545SGPIPAV4788103.3761053TACGTGGACGACAACAGTCGC3546YVDDNSR4789103.351054TTGACTCGGGGGGTCGCCGCA3547LTRGVAA4790103.3341055TCTGAGAAGGAGGCTCGGCTG3548SEKEARL4791103.3261056TCCACAACGCCTCCCTTCAAA3549STTPPFK4792103.3081057TACTCGACAACCATGCTTAAC3550YSTTMLN4793103.2991058AAAAACGGTGTTATAAACGAC3551KNGVIND4794103.2921059TTCGGTATAGGGCACGGAACA3552FGIGHGT4795103.2781060CCTCTTCATGTTGCTTCTCCT3553PLHVASP4796103.2451061TTGGGTAATGGTAGTTCTTTG3554LGNGSSL4797103.2391062AGTGGCAACGCGAACATAGTA3555SGNANIV4798103.2251063GGGATTAATCGTACTAGTGAG3556GINRTSE4799103.191064TCGGATAATAGGAATACTGCG3557SDNRNTA4800103.191065CGATTAGGAACCGTCACCAAC3558RLGTVTN4801103.1891066GTGGAGCATGTTGCTCATCAG3559VEHVAHQ4802103.1851067TATACTAAGCATCCTGTTGAG3560YTKHPVE4803103.1721068TCCCGAATCACGGTGAACGCA3561SRITVNA4804103.1541069ACAGTATCGTCATACGTACAA3562TVSSYVQ4805103.1341070CGCGCCGAAGGGAGCTCTGGC3563RAEGSSG4806103.1271071GCTGTGGGGCGGTCGGATGAT3564AVGRSDD4807103.1191072CGCATAGGCGTTGGAGCACCA3565RIGVGAP4808103.1131073TACTCAAACCTCGTACTTTCC3566YSNLVLS4809103.0951074TCGACGAATTCTGAGGCGGTT3567STNSEAV4810103.0681075GCAATGTCAACCCACATGATA3568AMSTHMI4811103.0671076AGGGTTGATATTTCGCATTTT3569RVDISHF4812103.0491077ATTCTTACGCCTTTGGATAAG3570ILTPLDK4813103.0391078GTTGCGAGTACGACGCAGACT3571VASTTQT4814103.0331079GACCGTAGCTCCGCGACGCTC3572DRSSATL4815103.0141080GATCATAGTGAGCAGAATTCG3573DHSEQNS4816102.9951081ATACGCAGCGAATTGGAAGTA3574IRSELEV4817102.9691082GCGAATCTGGGTGATGTTGAG3575ANLGDVE4818102.9691083GAGCTTAAGGAGAGTCAGAAG3576ELKESQK4819102.9561084TCATACACAGCAGGAAGACCC3577SYTAGRP4820102.9531085GGACCAGCCTACAACCAAAGC3578GPAYNQS4821102.9241086CATGAGAGTCATTATGTTAGT3579HESHYVS4822102.9211087AATGGTAAGCTGGGTACGACT3580NGKLGTT4823102.9211088CTTCCGCCTGCGTCGGCGGGT3581LPPASAG4824102.9171089TTGTCGTATCAGACTGGTCAT3582LSYQTGH4825102.9161090GACAGCCAAATCACAAGACTA3583DSQITRL4826102.9091091AACGTATACGAAGGGCACCGC3584NVYEGHR4827102.9091092TTGTTTACTGCTGGGAGTACT3585LFTAGST4828102.8631093CTTGTGAATAATGATGGGACT3586LVNNDGT4829102.8611094GCGATGAATGTGCGGAGTGAT3587AMNVRSD4830102.8581095GCCAGCCTTGACCGCCTTCCA3588ASLDRLP4831102.8571096GGCTCTCGGAACGGACCCACA3589GSRNGPT4832102.85321097ATGAGTGATGGGCATTCGAAG3590MSDGHSK4833102.8331098TCTAACCGTACGGAAATGCCA3591SNRTEMF4834102.8151099AACGTGGTGAAAAACAACACA3592NVVKNNT4835102.8011100GTGGTCGACTCAACATACCCG3593VVDSTYP4836102.7931101GTGGCTGGGGGGACTTCGGAG3594VAGGTSE4837102.7891102CGGGCAGACATGACTCCCTTA3595RADMTPL4838102.771103GGACACGAACAAACTGACGCA3596GHEQTDA4839102.7641104AGTGCTTTGATTAGTGTGGTT3597SALISVV4840102.7561105AACTCGACAACGGCACAATCA3598NSTTAQS4841102.751106TACGGCGACCTAACTACAGTC3599YGDLTTV4842102.7371107GCACGCAACGACGGACAAGGA3600ARNDGQG4843102.7341108CTGAACGTTAGTTCATCCAAA3601LNVSSSK4844102.6931109TCTGGCGTCTCGAAAGAACGG3602SGVSKER4845102.6921110AACATGGAACACACCATGGCG3603NMEHTMA4846102.6871111GCTCGTCCGGCTTCGTCTGAT3604ARPASSD4847102.67051112CTTAGGGAAGAATCTGCACGT3605LREESAR4848102.6391113TTGGCCAACATGTCCGCACCA3606LANMSAP4849102.611114AACCACACGGTAGAAGGACGC3607NHTVEGR4850102.5981115CCTCAGCATCAGCATGAGCAT3608PQHQHEH4851102.5821116AATTCTTCGGAGCTGAAGACG3609NSSELKT4852102.5641117CTTGTTGCTGAGCGTTTGCCG3610LVAERLP4853102.5521118AACGTTATGCACTCTTCCTCC3611NVMHSSS4854102.5251119GCGAGTGATAAGGGGGCGAAT3612ASDKGAN4855102.5091120AGTCTGGATCGGAAGCCTCCG3613SLDRKPP4856102.50321121ACAGAACACGAAAAATCCACT3614TEHEKST4857102.4591122CCTCATAATCAGGAGATGGGT3615PHNQEMG4858102.4491123GAGTCTAAGACTGTGGTTATT3616ESKTVVI4859102.4421124TCGACGGGCCAAAACTTAAAA3617STGQNLK4860102.4421125GTTCTTCATGTTTCTGATGTT3618VLHVSDV4861102.4411126CCTGACGCAGCGCGTAGCCCG3619PDAARSP4862102.4211127GCTCCTCGGCATGCTCATCCT3620APRHAHP4863102.4141128CATGTGAATCCTACGCCGGCG3621HVNPTPA4864102.4011129TTGCCTAATGAGCGTCCGGGT3622LPNERPG4865102.3971130GAGGCTAAGGGTTTTGGTCAT3623EAKGFGH4866102.3951131TCAGAAAACACCTCTGTACCC3624SENTSVP4867102.3881132GGTCCCGGAGAAAACTACCGA3625GPGENYR4868102.3751133TCTCATGAGATGAATAATGGT3626SHEMNNG4869102.3661134GTAGACACCTACAGCGGTCTG3627VDTYSGL4870102.351135GGAGTCCTAGGAAACATGGTA3628GVLGNMV4871102.3251136GCGCTGGATAATAGTAGTCGG3629ALDNSSR4872102.3221137TTTCTGGGTTCTAGTAATCAT3630FLGSSNH4873102.3211138CCTGTGGTTCATGGTGAGCCT3631PVVHGEP4874102.31421139CGCAGGGAAGGTATCCTAATG3632RREGILM4875102.3051140CAGCAGGGGGCGCCTACTTCT3633QQGAPTS4876102.3031141AAGGTTAGTGGTGGGGAGACG3634KVSGGET4877102.2751142GCGAAACACGAAAGCTCGTCT3635AKHESSS4878102.2721143ATTCTTATGGGTGCGCGTACT3636ILMGART4879102.2351144ACGCTAGGCAGCAGCAGCACC3637TLGSSST4880102.2221145CTAAGATCTGAACCGACACAA3638LRSEPTQ4881102.2181146CGCTCGGAACAAAAAACTCCG3639RSEQKTP4882102.2071147CACGCTCCAAGCGGCGCCATA3640HAPSGAI4883102.21148AGTAGTGTTACTTCGAGGGAG3641SSVTSRE4884102.1971149GTGAATCCGCATCCTGCGCAG3642VNPHPAQ4885102.1851150CAATACTCGATGGACACGCGC3643QYSMDTR4886102.1731151ACTCCTGGTGTTACTAGGACG3644TPGVTRT4887102.1721152CTTTATGAGGTTGGTACTCCT3645LYEVGTP4888102.1651153ACGATGACGAGTGAGCTTTCG3646TMTSELS4889102.161154TCAGGTTCGGAATACCGTACC3647SGSEYRT4890102.1531155GAAATGCAAACCAAAAACGCC3648EMQTKNA4891102.1441156GGCCACGAAAACATGGGCGTG3649GHENMGV4892102.1351157GGGGCGCATACGTCGGCTTCG3650GAHTSAS4893102.1161158GCTGATACGCTGCTGCGTAGG3651ADTLLRR4894102.0951159GACAACAGCAACAACGTCCCA3652DNSNNVP4895102.0921160ATGACTGCTAACTTGGTGGAA3653MTANLVE4896102.0761161GAAGCGGGACGCACGCTTCAA3654EAGRTLQ4897102.071162AGACACGTCGTCCCCGACTCC3655RHVVPDS4898102.0391163GTGAGTTCTGAGCAGTATAGG3656VSSEQYR4899102.031164GGTATCGAAGCAAGTCGCGGA3657GIEASRG4900102.0081165AGACAAGGCGTGAACGGAGTA3658RQGVNGV4901101.9911166ACTGTGATGATGAGTACGAGG3659TVMMSTR4902101.9761167TGGCAAGACCACAACAAAGTC3660WQDHNKV4903101.9481168GGAATCACAGGATCAACAGGA3661GITGSTG4904101.9431169AATTATGCTCAGAGGGATGGT3662NYAQRDG4905101.9361170AAACAAGAAGCTCTGTCCTCA3663KQEALSS4906101.8721171TCAACTTTAGACCGAAGCGAA3664STLDRSE4907101.86651172GCGATTACGAATACGCAGCAG3665AITNTQQ4908101.86151173AGGCTGGCGACTCAGAGTGCT3666RLATQSA4909101.8471174TGGCAGCTTACGACGAGTCAT3667WQLTTSH4910101.7751175GGTGGTAGTGGTTCTAATACT3668GGSGSNT4911101.7591176AACTTAGTAGCGTACACGAAA3669NLVAYTK4912101.7321177AAGGCTTCGCATGATACTAGT3670KASHDTS4913101.7211178GCCATAACGATAATAGGCACT3671AITIIGT4914101.7111179AACGCATCGTCGGACCGCTTC3672NASSDRF4915101.6861180GAAACGCAACGTATCGAACTG3673ETQRIEL4916101.6361181GTGATTGAGGTTAATTCGCGT3674VIEVNSR4917101.6141182GATAGGGATATGGAGGGTGTT3675DRDMEGV4918101.6091183ATTTCGGAGATGACGCGGTAT3676ISEMTRY4919101.591184GAGCATGATGTGAGTACGCGT3677EHDVSTR4920101.5391185CGTATGGAGGAGACTGCTTAT3678RMEETAY4921101.5331186TATAGTACTGATCTTAGGATG3679YSTDLRM4922101.521187GTGCCTGAGCCTAAGAAGGCG3680VPEPKKA4923101.4951188ACTTATGCGCCTAGGTCGCCT3681TYAPRSP4924101.4841189GCTGCGGCTTCGCCTTTGGCT3682AAASPLA4925101.4841190AGTGGGACGTATGCTAGTCGT3683SGTYASR4926101.4561191ACTGAAGCATCAATCGCGGCG3684TEASIAA4927101.4561192CGCATCGTAGACACGTTGGGA3685RIVDTLG4928101.4471193TATCTGCAGGAGAAGTTTCCT3686YLQEKFP4929101.4371194GTTCATGATCAGGGGGCTGGG3687VHDQGAG4930101.4361195CCCCAAGCCACTCTCAACAAC3688PQATLNN4931101.4321196TGCGGAATGTCCGAATGCTCG3689CGMSECS4932101.4291197GGTTCGCACAACGGGCCGACA3690GSHNGPT4933101.4291198TTTGGGTCTGGGCCGAATCTT3691FGSGPNL4934101.4131199ATGGATACGAATACGCATCGT3692MDTNTHR4935101.4111200AAGAATAATCCTGAGGATGGT3693KNNPEDG4936101.411201CTGCCTACGGCTACTGGTCAG3694LPTATGQ4937101.4061202ACGGCTGAGCGTACTGAGTAT3695TAERTEY4938101.3831203AACTACAGGGACATCACAATG3696NYRDITM4939101.3751204CCCGCGAGAAGCGACGCCCTT3697PARSDAL4940101.3591205TCCGTTGTAACTCTTGGGGTG3698SVVTLGV4941101.3241206GTTGTTAAGGAGATTAAGCTG3699VVKEIKL4942101.3241207GACCACTCGAAACAAAACTCT3700DHSKQNS4943101.2931208CAGTCTAATTTGGTTATTAAT3701QSNLVIN4944101.2921209ATTCCGGTTGGGGCGATGGCT3702IPVGAMA4945101.2861210ACGTCGGAGATGCGTACTGCT3703TSEMRTA4946101.2551211GGTAGTCAGCGTGCTATGAAT3704GSQRAMN4947101.2511212CACCTGTCACAAGCAAACCAC3705HLSQANH4948101.241213GGAGGGAACTCCCACGGGGTA3706GGNSHGV4949101.2191214GTGACTCGTAGTACGAAGGAG3707VTRSTKE4950101.1781215ATGCTCAGAGCAAGCACCGCC3708MLRASTA4951101.1711216GGCAGGCAAATACCAGAACAA3709GRQIPEQ4952101.1461217TGGAATCAGAATGTGTCTCAT3710WNQNVSH4953101.1251218CAGCGGGGGGAGCTTCCTGCG3711QRGELPA4954101.1141219GCGAATGATAGTTTGCGTTCT3712ANDSLRS4955101.0791220AACATGCCACCGGAATCGCAC3713NMPPESH4956101.0371221AATTTGAGTCTTCAGAGTCTG3714NLSLQSL4957101.031222ACATCAGACGGTCTACTAAGT3715TSDGLLS4958101.0281223GCGGGCCAAGCGTACCAATCC3716AGQAYQS4959101.0161224CTGAGTGTGAAGGAGGAGATT3717LSVKEEI4960101.0071225GATAATAGTCCTGCTAATCAT3718DNSPANH4961100.98121226ATGCACAACCTACCCTCATAC3719MHNLPSY4962100.96291227TACCAAGCCTCAAACAACAGT3720YQASNNS4963100.95941228GCGCGGGCAGAAGGGGTCTTC3721ARAEGVF4964100.93251229GGCCGAGAAGGAAACCTACCA3722GREGNLP4965100.9131230CAAGCTGCAGAAAGGGACAGA3723QAAERDR4966100.88771231GTTGAGAATAATCGTATGAGT3724VENNRMS4967100.81831232AATATGTCGCATAGTACTCTG3725NMSHSTL4968100.77041233TCTTCGTTGGGTCTTGCTCCG3726SSLGLAP4969100.72491234AACGTCGCTCCCTACAGTAGC3727NVAPYSS4970100.70691235AGGCCTGCGCAGCTGCCTGAG3728RPAQLPE4971100.6151236ATGTCGGGTTCTGGGAACGCA3729MSGSGNA4972100.5971237CACGGGGGGGAACACCGGAAC3730HGGEHRN4973100.57931238GCATCCGGCGCACGCTACGTC3731ASGARYV4974100.53021239CAAAACCACGCGTCTGGTGAA3732QNHASGE4975100.4991240GCACACCAAAAAGACCTACGC3733AHQKDLR4976100.45291241TTTGGGAAGGTTGGTACTGCT3734FGKVGTA4977100.4331242CTGCAGAAGTCGACTCTGGCT3735LQKSTLA4978100.34391243ATTCATAATGAGTCTTATGGT3736IHNESYG4979100.15TABLE 3MHCK7 / CK8 Combined Results mRNA Second Round of Capsid VariantSelection in C57BL6 mice-score capped at 100VariantID forSEQ IDAmino AcidSEQ IDSum of muscle mRNATableNucleotide SequenceNO:seq.NO:score_capped at 1001AGGGGTGATCTTTCTACGCCT4980RGDLSTP6647856.35252AGAGGCGACTTATCCACACCC4981RGDLSTP6648732.6723AGAGGAGACTTGACAACCCCA4982RGDLTTP6649683.3734AGGGGCGACCTGAACCAATAC4983RGDLNQY6650680.62655CGGGGTGATCAGCTTTATCAT4984RGDQLYH6651624.39156AGGGGGGATGCGACGGAGCTT4985RGDATEL6652620.57CGAGGAGACACCATGAGCAAA4986RGDTMSK6653599.4978CGGGGTGATCTTAATCAGTAT4987RGDLNQY6654579.7319CGGGGTGATCTTACTACGCCT4988RGDLTTP6655531.152510CGCGGCGACATGATAAACACC4989RGDMINT6656528.240511CGGGGGGATACTATGTCTAAG4990RGDTMSK6657469.507512CGAGGCGACACAATGAACTAC4991RGDTMNY6658412.324713CGGGGTGACGCAACAGAATTG4992RGDATEL6659408.086514CGTTTGGACCTGCAAGTCCAC4993RLDLQVH6660397.17815CGTGGTGATGTGGCGGCTAAG4994RGDVAAK6661395.17416AGGGGCGACCTCAACGACAGC4995RGDLNDS6662360.453517CGTGGGGATTTGAATGATTCT4996RGDLNDS6663349.683518TCTTATGGTAATACTCATGAT4997SYGNTHD6664326.82619CGTTTGGACCTGCAAGTCAAC4998RLDLQVN6665317.7820AAAGCGGGACAACTAGTGGAA4999KAGQLVE6666317.02321GATCAGACGGCTAGTATTGTT5000DQTASIV6667313.22422TATATTGCTGCGGGTGAGCAG5001YIAAGEQ6668308.73823GCGGTTGTTCTGAATAGTAAT5002AVVLNSN6669307.844524TCTAAAGGAAACGAACAAATG5003SKGNEQM6670305.01625GCAAACCCCAACATACTAGAC5004ANPNILD6671302.0226CACAACAAACCAAACGGAGAC5005HNKPNGD6672297.85127GATAAGACTGAGATGCTGCAG5006DKTEMLQ6673294.65528ACAGAACAATCTTACTCACGA5007TEQSYSR6674290.355529ACTGTGATGATGAGTACGAGG5008TVMMSTR6675289.394530GTCTCTACATACCTCCTGGCA5009VSTYLLA6676286.85931CCTAATGTTACGCAGTCTTAT5010PNVTQSY6677285.17832ATGAGTAATTTGGGGTATGAG5011MSNLGYE667828433ACGATGGGTGCTAATGGTACT5012TMGANGT6679278.29134AATGTTAATGCGCAGAGTAGG5013NVNAQSR6680275.4535GACCAAAACTTCGAACGTAGA5014DQNFERR6681274.604536AACACGTACACACCGGGAAAA5015NTYTPGK6682273.8354537CGTGGGGATATGATTAATACG5016RGDMINT6683270.33338GCACAATTCGAATCAGGCCGA5017AQFESGR6684267.734539ACGGCGTATCAGGCTGGTCTG5018TAYQAGL6685267.05440AGTGTTAGTTCTGTGGTGTTG5019SVSSVVL6686266.9141GGGCTTTCTAAGGCGTCTGAT5020GLSKASD6687266.82542TGGAACGGAAACGCCACACAA5021WNGNATQ6688265.1143ACAGCCGGCGGCGAACGCGCC5022TAGGERA6689258.78544TACACCTCTCAAACCAGCACT5023YTSQTST6690258.181845GCGAACATAGAAAACACGTCA5024ANIENTS6691257.01546GAACTCTCCGTTCCGAAACCA5025ELSVPKP6692255.13347GATCCTGGTCGGACGGGTACG5026DPGRTGT6693254.748GATCGTCCGAATAATATGACG5027DRPNNMT6694254.38349TATAGTACTGATCTTAGGATG5028YSTDLRM6695252.14650CAGTCGGTTAATAGTACGAGT5029QSVNSTS6696251.50851GCGGCACAACTCGTCAGTCCA5030AAQLVSP6697250.41352CTCGGAGGAAACAGCAGGTTC5031LGGNSRF6698247.977553GCGACGCTGAATAATAGTTAT5032ATLNNSY6699247.295554CGCTTGGACGTTGGAAGCCCG5033RLDVGSP6700245.83955TATCGGGGTAGGGAGGATTGG5034YRGREDW6701244.8356AGGGGAGATCTTTCTACGCCT5035RGDLSTP6702243.2557AGTGGTCTTTCGCATGGTCAG5036SGLSHGQ6703242.48658GAACACGCTACAGCAAAACAA5037EHATAKQ6704241.81659GGGGCGGAAGCGGGCCGCCAA5038GAEAGRQ6705241.4634560ATAAGCGGTTCCACTACACAC5039ISGSTTH6706240.881161GGCACCGTCGTTCCGGGCTCC5040GTVVPGS6707240.845562CATAATAATAATATGCTGAAT5041HNNNMLN6708239.075563CGTCTGACTGATACTATGCAT5042RLTDTMH6709238.93964AACACCTACCCCTTCAACGCC5043NTYPFNA6710235.8965TCAACCACTACTGGCCACATG5044STTTGHM6711231.58166GTGCATAATCCTACTACTACG5045VHNPTTT6712231.553767AATCTGCAGGTGAATGCGAAT5046NLQVNAN6713231.17268AGATACGGAGAATCCATCGAA5047RYGESIE6714230.6669AATACTACTCCGCCTAATCAT5048NTTPPNH6715230.22570AATACTTTGCAGAATAGTCAT5049NTLQNSH6716229.066671AGTCTGAACAACATGGGATCG5050SLNNMGS6717228.915472AGAAACGAAAACGTAAACGCT5051RNENVNA6718228.82873GCTGTGCATGCGACTAGTAGT5052AVHATSS6719227.88274ACCCAACACCTACCATCCACA5053TQHLPST6720227.084575AGTGTGTTGTCTCAGGCTAAT5054SVLSQAN6721225.403576AGTAGCTCAACTGAAGGGCAA5055SSSTEGQ6722224.97177GGTCGGACGGATACTCCTAAT5056GRTDTPN6723224.94578GTTCAAACCCACATAGGAGTC5057VQTHIGV6724224.61679ACTTCTGCTAGTGAGAATTGG5058TSASENW6725224.60880GGAAAAGCCAACGACGGTTCT5059GKANDGS6726224.593581GTGGAGCGGAATACTGATATG5060VERNTDM6727223.997582CAAAACCACGCGTCTGGTGAA5061QNHASGE6728223.87183TATTATGAGAAGCTTAGTGCG5062YYEKLSA6729222.172584TTCATCGCTAACACTAACCCA5063FIANTNP6730221.7685ACCTCCACGGCTTCAAAACAA5064TSTASKQ6731221.61786AATAATGATAATGGTTTTGTT5065NNDNGFV6732220.6187GCTAATTCTATTGGGGGTCCG5066ANSIGGP6733220.30488ACTGGCCAATTAGTAGGAACC5067TGQLVGT6734220.26289TACAGTCAATCGCTGTCTGAA5068YSQSLSE6735220.0290GTCTACAACGGCAACGTAGTA5069VYNGNVV6736219.82491AACTCGGCTGAATCCTCGAGA5070NSAESSR6737219.541592ACGCGTAATTTGTCTGAGAGT5071TRNLSES6738218.91993TCTATGTCTGATGGGCTTCGG5072SMSDGLR6739218.86894GTAGGCGACCAATCCCGCCCG5073VGDQSRP6740218.856595TTTACGGTGAATCAGGATCTT5074FTVNQDL6741218.06996TATCATAAGTATAGTACGGAT5075YHKYSTD6742217.6497TATGGTGTGCAGGCGAATAGT5076YGVQANS6743217.29398TTGCAGACGCCTGGGACGACG5077LQTPGTT6744217.17999TATCAGCAGACTTCTAGTACG5078YQQTSST6745216.8135100CAAACGAACACCAACGACAGA5079QTNTNDR6746216.664101ATGGATAAGTCTAATAATTCT5080MDKSNNS6747216.638102CATCTTAGTCAGGCTAATCAT5081HLSQANH6748216.575103GTTGGTGCGAGTACGGCTTCG5082VGASTAS6749215.9195104CACAACAACAACCTGCAAAAC5083HNNNLQN6750215.084105AGTACTTATGGGAATACTTAT5084STYGNTY6751214.971106CGGGCTGATGTTTCTTGGTCT5085RADVSWS6752214.499107CGAGGAGACAACAGCACACCG5086RGDNSTP6753214.29108GGTCGGGATTATGCTATGAGT5087GRDYAMS6754214.166109CCTAACAACGAAAAAAACCCG5088PNNEKNP6755214.048110GATAATGTGAATTCTCAGCCT5089DNVNSQP6756213.6615111ATGGGGACTGAGTATCGTATG5090MGTEYRM6757213.606112AATCAGAGTATTAATAATATT5091NQSINNI6758213.36113GCCATAGACTCTATCAAACAA5092AIDSIKQ6759213.304114GTTGAGTCTTCTTATTCTCGG5093VESSYSR6760212.9405115GGTCAGTATAGTCAGACGCTT5094GQYSQTL6761212.242116ACCATCCAAGACCACATAAAA5095TIQDHIK6762212.116117AACAGTTCCCAATGGCCCAAC5096NSSQWPN6763211.938118ACGGATAATGGTCTTCTTGTG5097TDNGLLV6764211.787119GTAAGAGAAACCACACACCTC5098VRETTHL6765211.44120CGTGGTGATATGACTCGTGCG5099RGDMTRA6766211.181121ACTTATGGTATTACTCATGAT5100TYGITHD6767210.641122ACGGCGCTGAATACGTATCCT5101TALNTYP6768210.568123GGTGGCGAAAACAGAACCCCA5102GGENRTP6769210.4124TATCTGCAGGAGAAGTTTCCT5103YLQEKFP6770210.3715125CTTAATCTTACTAATCATAAT5104LNLTNHN6771209.727126GGATTAGCTAGTCTACACCTG5105GLASLHL6772209.3585127GTAGAACACGTAGCCCACCAA5106VEHVAHQ6773209.322128AGCGAACACCACGCCGGAATA5107SEHHAGI6774209.188129GAAGCGTCCAACTACGAACGA5108EASNYER6775208.926130CCCTCCAACAGTGAAAGATTC5109PSNSERF6776208.6635131TCCCCCGGCAACGGGTTGCTA5110SPGNGLL6777208.4985132ATACTGAAATCCGACGCACCA5111ILKSDAP6778208.297133TTTGATAGTGCGAATGGTCGG5112FDSANGR6779208.26134GATGGTAAGACTACGTCTAAT5113DGKTTSN6780207.768135ACTAATTATCCTGAGGCGAAT5114TNYPEAN6781207.706136CGAGGAGACCACAGCACACCG5115RGDHSTP6782207.4315137CAGACGACTATTCTGGCTGCT5116QTTILAA6783207.223138GCTACTGCGCATCAGGATGGT5117ATAHQDG6784207.212139CAAGCCCTGGCCACCACAAAC5118QALATTN6785207.096140TATAATGCTACTCCTTCGCAG5119YNATPSQ6786206.964141GAGCTGTCTACTCCTATGGTT5120ELSTPMV6787206.8655142ATTAATATTAGTAGTGATTTT5121INISSDF6788206.753143GTAACGGCACACCAATTATCC5122VTAHQLS6789206.7385144GGAGAAAGCTCCTCAATAAGC5123GESSSIS6790206.656145GAATCCCTCCCAATCTCTAAA5124ESLPISK6791206.576146ACGAATGTTAGTACGCTTTTG5125TNVSTLL6792206.455147TGGCAGACGAATGGTATGCAG5126WQTNGMQ6793206.4378148TACAGGATGGAAACGAACCCA5127YRMETNP6794206.121149ATAACCGGCAACACCGTCGGA5128ITGNTVG6795205.9135150CTGAACACTCTAATCCACAAA5129LNTLIHK6796205.873151GGGACTTCCTTGGAAAACCGA5130GTSLENR6797205.8535152TACCAACACAACCAAGCCCAC5131YQHNQAH6798205.473153ATTGAGAGTAAGACTGTGCAG5132IESKTVQ6799205.0365154TATACGCAGGGTATTATGAAT5133YTQGIMN6800204.5275155AGTACGAATGAGGCTCCTAAG5134STNEAPK6801204.522156TTGTCTCAGAATTTTAATCCT5135LSQNFNP6802204.3926157TACTCTTCTGAAATGAGCGAA5136YSSEMSE6803204.31158TCATACGGAGGATCTGGCCCC5137SYGGSGP6804204.28159ATGGACGCTGCGTACGGTAGT5138MDAAYGS6805203.959160CCTTTTAATCCTGGGAATGTG5139PFNPGNV6806203.2041161CAAAAATCGGAAACCTACACT5140QKSETYT6807203.1248162AACAAAGACCACAACCACCTG5141NKDHNHL6808202.8605163CTAACCGGCTCTGACATGAAA5142LTGSDMK6809202.379164TCTAAGGATAGTACTATGTAT5143SKDSTMY6810202.335165GAAGCATTCCCGCGAGCGGGC5144EAFPRAG6811202.275166GAACACACTCACTTAAACCCG5145EHTHLNP6812201.959167AGTTCGGACCCAAAAGGTCAA5146SSDPKGQ6813201.825168AAAACCATCGACATAGCACAA5147KTIDIAQ6814201.699169ACCGGTAGCTTGAACTCTATG5148TGSLNSM6815201.671170ATGCAACGCGAAGACGCGAAC5149MQREDAN6816201.523171GCCTCTACAGTCTCACTCTAC5150ASTVSLY6817201.407172GGCCGTGACGACCTCACAAAC5151GRDDLTN6818200.911173TCTAATCCGGGTAATCATAAT5152SNPGNHN6819200.872174GATACTTATAAGGGTAAGTGG5153DTYKGKW6820200.7787175CCACCCAACGGCAGCAGTAGA5154PPNGSSR6821200.32615176GCTTCTTATAGTATTTCTGAT5155ASYSISD6822200.269177GTGACTGTTAGTCTGGATGGG5156VTVSLDG6823200.021178ATGGCCATAGGCCACTCCCCA5157MAIGHSP6824200179TTTCGGACGGTGTATACTGGT5158FRTVYTG6825200180AAAAAACGGCAGCCCATCGCC5159KKRQPIA6826200181AAAAATAAGCTCTACTATGGC5160KNKLYYG6827200182TCTACATCTCCGGTTAACAGC5161STSPVNS6828200183GGGTCTGGGATTGCGGGGACT5162GSGIAGT6829200184ATCGACGTACTGAACGGAAGT5163IDVLNGS6830200185GGTCATAATATGGCACAGGCG5164GHNMAQA6831200186ACGAGGAGCAACTCCGACGAA5165TRSNSDE6832200187GGAGCAAAAGGAACCATGGGC5166GAKGTMG6833200188GCTACTACTCTTACTGGTGAT5167ATTLTGD6834200189TTCAACACATCGTCGGAATTC5168FNTSSEF6835200190TATACGGCGCAGACCGGCTGG5169YTAQTGW6836200191CGAGTAAACAACGACGCAATA5170RVNNDAI6837200192ACTATTCAGCTTACTGATACT5171TIQLTDT6838200193GCCAGCATGCCCTCTGTAGAC5172ASMPSVD6839200194AATCAGGTGGGTGCGTCTGCG5173NQVGASA6840200195GGAAACATGGTGACTCCAAAC5174GNMVTPN6841200196CGTGGTGACCAAGGCACACAC5175RGDQGTH6842200197TCGAGTGATTCTCGTATTCCG5176SSDSRIP6843200198GGACTGCACGGCACCAACGCA5177GLHGTNA6844200199TCTAGTTATCAGTCTGGGCTG5178SSYQSGL6845199.609200ACAGCCTACTCGCCCACAGTC5179TAYSPTV6846199.236201CGCAGTGACACCACTAACGCC5180RSDTTNA6847198.59202CGTATTGTGGCTAATGAGCAG5181RIVANEQ6848197.795203ATCCACAACGAATCATACGTC5182IHNESYV6849197.72204CAGCAGAATACGCGTTTGCCG5183QQNTRLP6850197.4665205GGTATCAACTCCTCACACTTC5184GINSSHF6851197.224206GGTATGACTTCTAATCAGGTT5185GMTSNQV6852196.916207AGGGAGATTGTTCATAGTAAT5186REIVHSN6853196.5775208GCAGAACACACGTACACGGTC5187AEHTYTV6854196.501209CCTGCTACGCTACACCTGACA5188PATLHLT6855196.1975210AAGCAGACTGATAGTAGGGGT5189KQTDSRG6856196.15211ACTATGGTAGAAGTACTGCCA5190TMVEVLP6857195.586212ATCCCAACCGGCCAAACTAGC5191IPTGQTS6858195.499213ATGATAAAAACCAACATGTTG5192MIKTNML6859195.198214GCGGAACGACCCACTAGAGAC5193AERPTRD6860194.842215CGGGATCTGGGGCAGACCGGC5194RDLGQTG6861194.34216AATGAGGGGCGTGTGCAGACT5195NEGRVQT6862194.00545217ACTGCGGCTAGTACTGCGAGG5196TAASTAR6863193.5855218ACCCAAGGGAACAACATGGTA5197TQGNNMV6864193.362219CATAGTACTTTTCCTACGACT5198HSTFPTT6865193.274220CAATCTATCGGCCACCCCGTT5199QSIGHPV6866191.64595221TCGGGTGTTAATAGTGAGCGT5200SGVNSER6867191.3763222CCTCACGCCAACGGAGTGACA5201PHANGVT6868191.349223GACCACCAACAAGCCCTAGCT5202DHQQALA6869191.305224AGTCAGCAGGGTTTTACTCTG5203SQQGFTL6870191.2955225ACAAACGCTGCTCTAGTACCA5204TNAALVP6871191.1973226GGTGTTAGTAGTAATTCTGCG5205GVSSNSA6872190.1595227CATGATACGGTTGGGGAGAGG5206HDTVGER6873189.859228GCGTTAAACGCCCAAGGGATC5207ALNAQGI6874189.3825229CATGATAGTATGTGTTGTGCG5208HDSMCCA6875189.35230TACATCGCGGCAGGGGAACAA5209YIAAGEQ6876189.046231GAGAATGCTCGTGAGGGTGTG5210ENAREGV6877188.331232GCTACGGTTTATAATGAGTTG5211ATVYNEL6878188.18233GACACTAACGGAATAAAATCA5212DTNGIKS6879187.628234AAGCCGACTGCGAATGATTGG5213KPTANDW6880187.4884235TATGAGAGTACTCATGTTAAT5214YESTHVN6881187.1195236TACACCAACGGGGGCCACCTA5215YTNGGHL6882187.0304237GTAGACAAATCTAGCCCAGTG5216VDKSSPV6883186.9365238CCAATCCAAAACGAATCGTCC5217PIQNESS6884186.748239ATACACAAATCTAGCGTCGAA5218IHKSSVE6885186.654240CATGATATTAGTCTGGATCGT5219HDISLDR6886186.65241TGGTGAGGGGCTGAGTTTGCC5220W*GAEFA6887186.1242TACTCTCAATCCATAAAAAAC5221YSQSIKN6888186.0095243GCCCAAGACAACAACCACGAC5222AQDNNHD6889185.6231244GGGCAGAAGGAGACTACTGCG5223GQKETTA6890184.948245AAAAGCGAAGTACCCGCCCGA5224KSEVPAR6891184.116246GAACTTAACACCGCACACGCA5225ELNTAHA6892184.059247AGCACAAACGCGGGACAAAGG5226STNAGQR6893183.7145248AAGGCGGTTTCGGAGATTATT5227KAVSEII6894183.539249ACCTTCACGGTCGACGGTAGA5228TFTVDGR6895183.2535250AGTACGAGTGGTTATAATACT5229STSGYNT6896182.703251AATCATAGTCTGTCGGAGCAT5230NHSLSEH6897182.427252TCTATGCAGGATCCTTCTTTG5231SMQDPSL6898182.375253GAACAACAAAAAACAGACAAC5232EQQKTDN6899182.331254GCTGTTGTGAATGAGAATATG5233AVVNENM6900182.3255GGTCCCGGAGAAAACTACCGA5234GPGENYR6901182.165256TACAACGCAGGCGGAGAACAA5235YNAGGEQ6902182.14257GTCCTCTCCTCCAACCTGTAC5236VLSSNLY6903181.3605258GGTCTTTATCAGAATCCTACG5237GLYQNPT6904181.2475259AGTTCGGGGAGTTTGATTACT5238SSGSLIT6905180.8125260TATAATACGGATCGGACTAAT5239YNTDRTN6906180.0485261GAGAAGCCTCAGCATAATAGT5240EKPQHNS6907179.9715262GCGGCTTATGAGCATGCGCCT5241AAYEHAP6908178.7065263GGCGGCAACTACAACACAACT5242GGNYNTT6909178.62264TATCTGAATAGTACGCAGATT5243YLNSTQI6910178.4905265TCTAATTCTAATACTGCTGCT5244SNSNTAA6911178.119266TCGGATAATAGGAATACTGCG5245SDNRNTA6912178.09355267CGCTCGTTGGACAGCGGGATG5246RSLDSGM6913177.6395268GTTATGGATACGCATGGGATG5247VMDTHGM6914177.54269CATGTTACGGCGGTGGTTGAT5248HVTAVVD6915177.447270AGTATCACCCACAGCAACACC5249SITHSNT6916177.4093271GGATACGGCAGTTACAGCAAC5250GYGSYSN6917177.0995272CGTTGGTCTGAAAACAACTCC5251RWSENNS6918176.788273ATGTCTAGCCACACCGTCCAA5252MSSHTVQ6919176.741274TATGTTAGGGCGCAGGATCAG5253YVRAQDQ6920176.713275TTTGAGGGTGATAAGACTTAT5254FEGDKTY6921176.655276GTTAGCTCCGGCCACACGAAA5255VSSGHTK6922176.4715277TCGATGAACCTGCCAACTTCA5256SMNLPTS6923176.425278CTGAATCCTCAGCATGAGTTG5257LNPQHEL6924176.19279CTTCCGCCTGCGTCGGCGGGT5258LPPASAG6925176.057280GGAGGGAACTCCCACGGGGTA5259GGNSHGV6926175.7625281GGGGGTACGGGGTTGTCGAAG5260GGTGLSK6927175.714282AGTTTGAATTCTTCGAGTACT5261SLNSSST6928175.4585283ATGCCTAGTGAACCACCAGGG5262MPSEPPG6929175.45284GTTGTGCATTCGAGTATTACT5263VVHSSIT6930175.18685285TTGAGTCTGGCTGGGAATAGG5264LSLAGNR6931175.0985286GCGGACATGCAACACACCGTA5265ADMQHTV6932175.003287TTTCGTGATGGTCAGGGTATG5266FRDGQGM6933174.983288ACCGGAACAGCGATCTCCCGA5267TGTAISR6934174.5465289ATGGGGAAGCATGAGGGTCTT5268MGKHEGL6935174.3418290CCGGAATCCGCCGCCAAAAGC5269PESAAKS6936174.268291ACCCAAGCCTTCTCCCTAGGC5270TQAFSLG6937174.2365292ACTGATGGTATTTTTCAGCCT5271TDGIFQP6938174.014293GGGAGCCCAGTGATAGTAAAC5272GSPVIVN6939173.652294GGGCGTGATAATCATCATGCG5273GRDNHHA6940173.4132295CCGCGTTCTATTACGGAGTTG5274PRSITEL6941173.403296TGGGTAAACAGTGTGGGCAAC5275WVNSVGN6942173.244297GTTCATGGGACGTTGACTTAT5276VHGTLTY6943173.1685298GGTGTGTATATTGATGGTCGG5277GVYIDGR6944173.081299ATGAGTAATGATTTGCCTGGG5278MSNDLPG6945172.671300AATCGGTCGGATAGTTTTGCG5279NRSDSFA6946172.6595301GGGCAAACAAACGCAGTACAC5280GQTNAVH6947172.4582302TACGTCGACAAATCAATGACA5281YVDKSMT6948172.1735303AGTGTGATGGTGGGTACGAAT5282SVMVGTN6949171.86304ATTGGTCTGCAGAATTCTACT5283IGLQNST6950171.84715305AACGACCGACCGCTTGCCAGC5284NDRPLAS6951171.464306CTCATGGGCAGTCCAGGCGCG5285LMGSPGA6952171.27307ATTGATCGTAGTGCTAGTTTG5286IDRSASL6953171.009308ATTCAGGCGAAGAATTCTGAG5287IQAKNSE6954170.983309CATCAGTCTTTTGATGCTGGT5288HQSFDAG6955170.699310GCGGTTAATGAGACTAGGCTT5289AVNETRL6956170.564311ATCGCGTCAACGTGGAACATG5290IASTWNM6957170.52312AAAGTGGACATGACCTCCAAA5291KVDMTSK6958170.4035313TCTCATAGTATTACGGGTCTT5292SHSITGL6959170.333314ACTATTACTAGTCCGTCGGTG5293TITSPSV6960170.18315GAACACATCTCTAGCTACGGA5294EHISSYG6961169.832316TTCTCAACAAACTCTGTAATC5295FSTNSVI6962169.7245317TCGATGGAGGGTCAGCAGCAT5296SMEGQQH6963169.71318GTCGACAAAAGCGAAGCCGTC5297VDKSEAV6964169.6265319CAAGCTAACTTATCAATAATC5298QANLSII6965169.3842320GTTAAGGCGAGTGCTGGGGTT5299VKASAGV6966169.1112321TTTGGTACTTCTTATACGACT5300FGTSYTT6967168.915322GGGCTCACAGGATACCCAATG5301GLTGYPM6968168.8625323GCTATGGGAGCACTCGTGCAC5302AMGALVH6969168.807324GTATACGCCACCGCACTCGCA5303VYATALA6970168.7005325ACATTAACAGACGTTCACCGA5304TLTDVHR6971168.7326CCATCCTCAGCGGGTAGCACA5305PSSAGST6972168.601327AAAAAACGAAAACACTAACTA5306KKRKH*L6973168.58328GCTTATCAGCTGACTCCGGCT5307AYQLTPA6974168.579329CTTGCGCCTGATAATATTGGG5308LAPDNIG6975168.515330ACAATCGTTTCCGCTTACGCC5309TIVSAYA6976168.3875331GGTAATAATTTGAGTTTGTCT5310GNNLSLS6977168.1503332AGCACAAACACCGAACCTAGG5311STNTEPR6978168.122333TCTTTTCAGACGGATCGTGCG5312SFQTDRA6979167.793334TTCTTAGAAGGAGTCGCTCAA5313FLEGVAQ6980167.647335CAAGACGTAGGACGCACGAAC5314QDVGRTN6981167.4595336ACGCATGGTGATCATATTCAG5315THGDHIQ6982167.197337GTATCAGAAGGACAACGAATC5316VSEGQRI6983167.049338AACATGGGTCCAATGGGCCGG5317NMGPMGR6984166.961339CTACCCTCAACAGAAACTTTG5318LPSTETL6985166.942340GGTGGTATGTCGGCGCATTCG5319GGMSAHS6986166.775341GGGATGATCGGGCACAACGCA5320GMIGHNA6987166.716342ATAGACGAACGTTCCTCGATA5321IDERSSI6988166.601343CATGTGAATCCTACGCCGGCG5322HVNPTPA6989166.586344TGGTCGAGAACTGGAAACACC5323WSRTGNT6990166.483345ATCAAAGACTCGTACCTTACT5324IKDSYLT6991166.205346TTGAACCAAAACAGTGTCTCC5325LNQNSVS6992166.174347TCTGGTCCGATTCCTGCTGTT5326SGPIPAV6993166.146348ATGCAAGGGCTTAACAACATG5327MQGLNNM6994165.268349TCAAACAGCGGAGGCAACCAC5328SNSGGNH6995165.1895350ACGAGTACGATGACTGCGCGT5329TSTMTAR6996165.115351GAGAATAGTGATTTGTCTTAT5330ENSDLSY6997165.08352CATCCTGGGAATAGTTCTGTG5331HPGNSSV6998165.062353TTAACACCCCAAGGGACTAGT5332LTPQGTS6999165.0315354ACCGACACCCGAAAAAACGAC5333TDTRKND7000164.843355GGGGAGACGCTGAGGTCTCAG5334GETLRSQ7001164.72165356AGCGGTGTATCAGAAGGAAAC5335SGVSEGN7002164.715357ACTCAGTATGGTACTCTGCCG5336TQYGTLP7003164.526358GGGACGGTTAACTCAAGTGCA5337GTVNSSA7004164.3765359GGTAAAGCAACCTTAGTCCTC5338GKATLVL7005164.3755360GGTATATACCCGGCATCCACC5339GIYPAST7006164.34361GGTGTTATGTCTAATGCTACT5340GVMSNAT7007164.06362ACTCATGTGATTGGGGCTGTG5341THVIGAV7008163.918363ACTCGGAGTGATATTGGTGTG5342TRSDIGV7009163.7255364ACGCTTACATTATCTACCCTC5343TLTLSTL7010163.5555365TATAATGAGTCTTCGAATGCG5344YNESSNA7011163.314366TCGACGCAGGCGCAGACCGGC5345STQAQTG7012163.15367CGCGACATGATCAACTCATCA5346RDMINSS7013162.984368ACTAAGGGTAATAATCTGGTT5347TKGNNLV7014162.899369GGTTCTACGGTGTCGGCGCAG5348GSTVSAQ7015162.631370AGGGGTGATACTATGAATTAT5349RGDTMNY7016162.425371CATGCGGATGTGAATGCTGGG5350HADVNAG7017161.99372AGCGTTGTCAACACCAACATC5351SVVNTNI7018161.9445373TCTAATGTTCATGTTGTTAAT5352SNVHVVN7019161.753374TCGGTTGATAAGCCGCCGGGG5353SVDKPPG7020161.487375GACCGCACCTACTCAAACACA5354DRTYSNT7021161.475376TACTCCGGAGAACTAAACAAA5355YSGELNK7022161.125377TATGATAAGACTTTGAGTGTT5356YDKTLSV7023160.90695378CACACCGCCACCCTTAGCAGC5357HTATLSS7024160.8605379GCTCTGGAGAGGGCTCAGTAT5358ALERAQY7025160.837380GGTACGAGTGATAATTATAGG5359GTSDNYR7026160.175381CATGTGAATAGTAGGGATCTT5360HVNSRDL7027160.127382TCGTCAGACGTTACCAGACAA5361SSDVTRQ7028160.07383GCTCATCATATGACGACGGAG5362AHHMTTE7029160.019384GAGGTGTCTAGGGATGGTCTG5363EVSRDGL7030159.7445385GTGGGCCGTGACGCAGAAGCT5364VGRDAEA7031159.58386GCACACCAAAAAGACCTACGC5365AHQKDLR7032159.3139387AGTGTTCTGAGTAGTTCGACT5366SVLSSST7033159.208388CTGGGTACGCTGCTTAGTCAG5367LGTLLSQ7034159.04389TCACAAAAACCAATCGACGAC5368SQKPIDD7035158.663390GATAATGTGCATGGGCAGGTG5369DNVHGQV7036158.321391GGTTCGCACAACGGGCCGACA5370GSHNGPT7037157.748392ATCTCCGGTAGTAGCAGTCTA5371ISGSSSL7038157.64393GGTTTTCATATTAATGGTGAG5372GFHINGE7039157.326394ATGAGTGATGGGCATTCGAAG5373MSDGHSK7040157.296395ACTGTTGGTGGTAATCATCAT5374TVGGNHH7041156.895396AATGCTACTCCGCCGAATCAT5375NATPPNH7042156.8609397ACGGGTATGAATAGTAATAAG5376TGMNSNK7043156.85398ATCGAAGCCTACTCACGAGAC5377IEAYSRD7044156.774399CGCGACCGTCAAGACTCGGTA5378RDRQDSV7045156.7165400CACACGGTTCAAATACGCGAA5379HTVQIRE7046156.6241401ACTTTGACGCAGACTGGGATG5380TLTQTGM7047156.5735402ATTAATAATTTTAATACTCTG5381INNFNTL7048156.48403GTAGCCGCGGGACCAGAAGCG5382VAAGPEA7049156.315404GATGGTAAGAATAGTTATGCG5383DGKNSYA7050156.294405TCCAGGCAAGAAAACTTCTCC5384SRQENFS7051156.182406TCTAACAGCAGTGTTGCGGTA5385SNSSVAV7052156.048407GATCATAGTAAGCAGAGTTCG5386DHSKQSS7053155.89425408TTGAGTGGTGCTGGTAGTCAG5387LSGAGSQ7054154.9295409GGTTGGAGTAATAATGAGTTG5388GWSNNEL7055154.4735410CTAATACGAGGTTCCATGGAA5389LIRGSME7056154.426411AATACTTATACTGCTGGTAAG5390NTYTAGK7057154.346412ACTCGTGGCGACATGGAATTC5391TRGDMEF7058154.246413CTCATGTCAGGGAAAGAAAAC5392LMSGKEN7059154.155414AAGGATACTAATCAGCAGATT5393KDTNQQI7060153.7595415CACAACGTCGGCCTAGGACAC5394HNVGLGH7061153.7416CCTGATCAGCCTGGTCCTTCT5395PDQPGPS7062153.51417ATGCAAAGAGAAGCAGCCAAC5396MQREAAN7063153.45418GGGCAGCGTACGACGAATGAT5397GQRTTND7064153.425419AAACACACAGAAAACGGGACC5398KHTENGT7065153.394420TTAGACGTGACGAGAATGAGA5399LDVTRMR7066153.086421ACGTTGGATCGGAATCAGACT5400TLDRNQT7067152.9552422ATCAACGCCGGCAACTACCGA5401INAGNYR7068152.8475423GCCGTAGACCAATCACGTTTG5402AVDQSRL7069152.8359424GCTCTTGGGCATCAGGGGAAT5403ALGHQGN7070152.467425CTTCCGCGTCATGATCAGTAT5404LPRHDQY7071152.412426ATTTCTGGGTCGTCGTCTCTT5405ISGSSSL7072152.2375427TGGAATACGAATATGGCGATT5406WNTNMAI7073151.8755428ATGTCGGATCGTACTTCTGAT5407MSDRTSD7074151.677429ACAAGGGAATCAATGTCCATC5408TRESMSI7075151.6105430CAGCGGGGGGAGCTTCCTGCG5409QRGELPA7076151.533431TCGTCTGATCCTAAGGGGCAG5410SSDPKGQ7077151.4265432CCGAGTGATAGGACTACTTAT5411PSDRTTY7078151.3695433TCTTCTTCTGATAGTCCGCGT5412SSSDSPR7079151.2845434GTATTACACTCTGTATCAGCA5413VLHSVSA7080151.217435AGTATGCAATCATACACCATG5414SMQSYTM7081151.1285436TCTCTGCAACTCACAGCGGGT5415SLQLTAG7082151.106437AACAACGTAAACCCGTACTCG5416NNVNPYS7083151.0935438CTTGCGAATGGTATGACGGCT5417LANGMTA7084150.9825439GGAATCACAGGATCAACAGGA5418GITGSTG7085150.979440ATGCTTGTTCAGAATACTCCT5419MLVQNTP7086150.943441GATGCGAATGCGGGTACGAGG5420DANAGTR7087150.871442GAAACCGGAGCTATGACCTCT5421ETGAMTS7088150.803443ATACAAACTACTACAAAATGC5422IQTTTKC7089150.692444GCGCAGCAGAGTCTTCATGGT5423AQQSLHG7090150.673445ATTGATAGTACTTGGAATACG5424IDSTWNT7091150.518446ACCGAATCGCAAACCATGAGG5425TESQTMR7092150.4394447TTGATCCAAACGCAAGGCACG5426LIQTQGT7093150.329448ATAGTAAACATAACTCAATCG5427IVNITQS7094150.305449GTGGCGGTGTCTAATACGCCT5428VAVSNTP7095150.03285450GGTCATAGGGATTCGGGTGGT5429GHRDSGG7096149.991451CGGAATGAGAATCTTAATAAT5430RNENLNN7097149.913452GTCATGCAACGATCTGCACAA5431VMQRSAQ7098149.77453GTCTCGGGTCCGGTATCGGTC5432VSGPVSV7099149.7645454GGGGATATTCAGAGTCATAGT5433GDIQSHS7100149.392455GTTGAGAAGCCTCTGGAGACT5434VEKPLET7101149.24456GGTGTTCAGATGACTGCGGGG5435GVQMTAG7102149.14805457ACCACAAAAACGACATCTATG5436TTKTTSM7103149.0935458CCTGGGAATCCGTCTAGTAAT5437PGNPSSN7104148.9075459GCTTCGCGGCCTGCGGCTCAG5438ASRPAAQ7105148.8831460GTTCATGATCAGGGGGCTGGG5439VHDQGAG7106148.829461TCAGGTTCGGAATACCGTACC5440SGSEYRT7107148.812462TACGTGGACGACAACAGTCGC5441YVDDNSR7108148.744463ATGGCCGGTGACCAAGAACTC5442MAGDQEL7109148.7464CCTTTGCACAACATACCTCCT5443PLHNIPP7110148.609465AGTGGGATTGGTACTTATTCT5444SGIGTYS7111148.357466TCGAACGCAGACATCCTCGCC5445SNADILA7112148.08467AGTCACAACCAAGTAAACGTA5446SHNQVNV7113147.981468CAGCATTCTCCGAAGCCGGTT5447QHSPKPV7114147.97469TCCGCAAACAACATAGCCCCC5448SANNIAP7115147.813470GAAGAAACACGGACCAGAATG5449EETRTRM7116147.667471CTGTCTAATTCGATTACGCCT5450LSNSITP7117147.594472AGTGCTTTGAATAGTGTGGAT5451SALNSVD7118147.326473ACTAATCTTGCTGTTACGCTG5452TNLAVTL7119147.1589474CAGTCGACGCTGAATAGGCCT5453QSTLNRP7120147.0302475ATAGAACACATGCTTAGACCC5454IEHMLRP7121146.9635476CCGACTCCTAATGAGCATATG5455PTPNEHM7122146.84477ATTAATGAGATTGGTAGGATG5456INEIGRM7123146.786478AACAACGACAACGTCTACGTG5457NNDNVYV7124146.764479ATAGTCCACACCCCGCAAGTG5458IVHTPQV7125146.309480CATAAGAGTGAGAGTCATAAT5459HKSESHN7126146.142481TCATCGTCAGACTCACCCAGA5460SSSDSPR7127146.067482TACTCTACAGAAGCACGAGTC5461YSTEARV7128145.9845483ACCTCGGGTGACCGGTACACG5462TSGDRYT7129145.963484GAGAAGAATCTGACTAATGCT5463EKNLTNA7130145.88775485ACAAGGGACCAAAGGTCTACA5464TRDQRST7131145.8855486GCGACTGATAAGATGACTCCT5465ATDKMTP7132145.881487AATAGTTATACTGCTGGGAAG5466NSYTAGK7133145.87565488ACGCTGGATACTAAGGATCTT5467TLDTKDL7134145.82489GCATCCAACGGGCAAGTTAAC5468ASNGQVN7135145.7395490ACCTCAATATCGTCGCAAAGC5469TSISSQS7136145.707491GATAATAGTCCTGCTAATCAT5470DNSPANH7137145.5712492AACTCCAGGGAAATGGGTGTA5471NSREMGV7138145.562493ACCAGCGCGTCTGAAAACTGG5472TSASENW7139145.56494ACTGTAGGATCCTCATACGCT5473TVGSSYA7140145.0453495CAACAATCACAAAACTCTATA5474QQSQNSI7141144.9825496CTTCGGGATGGGATTGCTTCT5475LRDGIAS7142144.9725497GTGCAAAAAACGACGGCTTGG5476VQKTTAW7143144.78498ATGAGTACGGTTCTTCGGGAG5477MSTVLRE7144144.5125499AGTATGGATGCTCGGTTGACG5478SMDARLT7145144.404500GGCGCCCGTACAATCTTAGAC5479GARTILD7146144.3975501CACGAAAGCCACTACGTGTCA5480HESHYVS7147144.2755502CTTGAGGGTCAGAATAAGACG5481LEGQNKT7148144.137503CGGGACTTGAGACCCGTGACG5482RDLRPVT7149143.788504CAGATTTTGAATTATAGTGTG5483QILNYSV7150143.741505ATAAGTGTAGGTGTGTCCGTA5484ISVGVSV7151143.727506AAGGCGGGTGAGTATAGGGAT5485KAGEYRD7152143.693507CTTACTACGAATGGTATGCTG5486LTTNGML7153143.66508ACTAGTAATTATATGCATGAG5487TSNYMHE7154143.642509ACCCACAACTCTACAGGCCTT5488THNSTGL7155143.502510AATAATGTTGTTAGGGATGAT5489NNVVRDD7156143.142511AGTGGGACGTATGCTAGTCGT5490SGTYASR7157143.123512CTGTCTCACGCCATGGACCGG5491LSHAMDR7158142.937513AATTGGAATTCTGAGGGTACG5492NWNSEGT7159142.7425514AGTCTGCGTCCAACCCTACCT5493SLRPTLP7160142.4292515TACCAAACGGGAGACAAAGAC5494YQTGDKD7161142.104516CGCAGCGACAAAGGAACGTTG5495RSDKGTL7162142.1004517TCTACCATCGGCAACAGCACG5496STIGNST7163142.0895518GAAAACAACATGCAACACGGC5497ENNMQHG7164142.037519AAGTATACGGAGTCGAATGCG5498KYTESNA7165142.0295520CCAACAAACAACTTAAGTATG5499PTNNLSM7166141.91521TGCAAAAACAACTCAGAATGC5500CKNNSEC7167141.874522ACGGTTAATGCGGATGGGTCG5501TVNADGS7168141.672523TTTTCTGGTCAGGCGTTGGCT5502FSGQALA7169141.6645524AATCATATTAGGAATCCTATG5503NHIRNPM7170141.628525ATGGTGAATTCGGAGAATACT5504MVNSENT7171141.624526ACTGATGGGCCGCGTCTGGCT5505TDGPRLA7172141.5814527TTCAACGGGTACGTCATGGCA5506FNGYVMA7173141.042528AATGCGAATGGGCCTGTGAGT5507NANGPVS7174141.0385529AGTACGAGTCAGGAGAATAGG5508STSQENR7175140.9233530CAAGGGACTCTCTTGTCTCCA5509QGTLLSP7176140.773531CTAATCACAGCCACCACTAAC5510LITATTN7177140.4315532TCTGGCGTCTCGAAAGAACGG5511SGVSKER7178140.3655533TCTACTTCAATAGGAGTGGTA5512STSIGVV7179140.351534TCTCATGTGACTGTTACGGAT5513SHVTVTD7180140.31535TCTAATAATCTGAATCAGGAG5514SNNLNQE7181140.282536GCAAACCACGACAACATCGTG5515ANHDNIV7182140.0405537GACACGTCCTCCGGCAACAGG5516DTSSGNR7183140.01538GTGGTTCCTATGCCTACTACT5517VVPMPTT7184139.945539CTTACTAATAATTTTAAGGAT5518LTNNFKD7185139.782540TCTTCGCCTACTAAGGGTACT5519SSPTKGT7186139.7594541GATATTCCGTCTGATAATACG5520DIPSDNT7187139.44542TACACGGGATTCGAATTGAGA5521YTGFELR7188139.43543AACTCAGGTAACAACCCCATC5522NSGNNPI7189139.4185544ACGACCCGAAACGAACACTCG5523TTRNEHS7190139.3175545AATGTGGGTAATACTCTTGGG5524NVGNTLG7191139.128546TACCACACCCACCAAGTCGCA5525YHTHQVA7192138.871547GGTAGTGCGAGTAATAGTGGT5526GSASNSG7193138.841548GGGAAGAATCAGCCTACTCCG5527GKNQPTP7194138.839549TTCACCGCCACTTTAGGAACC5528FTATLGT7195138.809550ATGAACCAAATGGGCGGCCTG5529MNQMGGL7196138.794551AACGTGTCACTAACGCAAACG5530NVSLTQT7197138.62365552TCGTCTAGCAACACAAACGCT5531SSSNTNA7198138.538553ACTAATTCTAATCAGAGTTCG5532TNSNQSS7199138.513554ATAAGTCACGACCTTAAATAC5533ISHDLKY7200138.4685555GATTCGACGTATGTTTTGGCT5534DSTYVLA7201138.402556ATGAACACCGGCTCTTCGAGT5535MNTGSSS7202138.35557GCCGGAAACTACCAATCATCA5536AGNYQSS7203138.2335558ACGATTTATAATATGGGTCCG5537TIYNMGP7204138.1385559GTATCAACGACAACGGACCGG5538VSTTTDR7205137.9925560GGGGTGACTGTTAGGGAGCTT5539GVTVREL7206137.96205561GATATTACTAATCAGTCGTAT5540DITNQSY7207137.802562AATCAGTCGCTTACTATGGAT5541NQSLTMD7208137.363563ACGAATTATAATATTGGTCCG5542TNYNIGP7209137.0645564CGTGGTACGGAGGGGACGCCG5543RGTEGTP7210137.0621565CCCATAACACGGGAATCGGGA5544PITRESG7211136.943566ACCGGACAAGCGGGCGGATCG5545TGQAGGS7212136.857567ATGACTAAACACGACGCGACG5546MTKHDAT7213136.624568CCTATACCCCACGGTTCATCC5547PIPHGSS7214136.299569ACGACTGGGGGGACGGGGATG5548TTGGTGM7215136.1295570CTAACCGAATCTGTGAGAAAC5549LTESVRN7216135.933571AGTAGTAATCTGACTTTGTCT5550SSNLTLS7217135.86572TTGAATAATTCTGCGACTGTT5551LNNSATV7218135.76573GCATACGGATCGTCCGGAAGA5552AYGSSGR7219135.5095574GTTTCTTATGATAATGGGTCG5553VSYDNGS7220135.48575CCGAGTCAGAGTAGGTCGCTT5554PSQSRSL7221135.38455576GTCCTGGTTAACGTACACAAC5555VLVNVHN7222135.346577TTGATGACTGGTACTGCGTCG5556LMTGTAS7223135.327578GCTGCTGGTAATCCTACTCGT5557AAGNPTR7224135.3067579TCCGCGCAATCTTTCGTAGTT5558SAQSFVV7225134.721580CAAGACCAAACGAGCAACCGT5559QDQTSNR7226134.721581CAGTCGATTGGGCATCCGGTG5560QSIGHPV7227134.625582GCTGGGGTGCGTGAGTCGTTT5561AGVRESF7228134.586583AATACTAATTATGCGATGCAT5562NTNYAMH7229134.493584GAGCGGAGTACGCATAATGTT5563ERSTHNV7230134.479585ATGTCCGGATCCATGATATCA5564MSGSMIS7231134.414586TCTGGCCAAGGATTCTCGGCA5565SGQGFSA7232134.3465587ACATTCACTACTCTGGGCAAA5566TFTTLGK7233134.2015588GACGCAAACGCTGGCACAAGA5567DANAGTR7234134.063589AGGGATACGGCTAAGGGGGTG5568RDTAKGV7235133.882590GTGCGGTCTGGTAATAAGCCG5569VRSGNKP7236133.87591CCCCAATGGGGAACTGACCCG5570PQWGTDP7237133.743592GCCTTCCAAAACACCGGCGCA5571AFQNTGA7238133.743593GCGACGACTCAGCTGATGACT5572ATTQLMT7239133.675594ACGAACGCGAGCGAAGGCTCA5573TNASEGS7240133.642595ATGCTCACAGAAACCAAAGCA5574MLTETKA7241133.57596ACGAATAATTTGCTGGCTCAG5575TNNLLAQ7242133.517597GATGTTTTGCTTAAGAATTTT5576DVLLKNF7243133.49598TATACGCCTGGGCTTACTGAG5577YTPGLTE7244133.356599CGGCATGCTTCGGATGCTAAT5578RHASDAN7245133.22600AGTAAGGGTGATCAGCTTAAT5579SKGDQLN7246133.1865601GTGCTGGTTACTCAGAATCAT5580VLVTQNH7247133.0645602CGACAAGGCGACTTAAAAGAA5581RQGDLKE7248132.97895603ATTCAGTCGCAGTCGCAGTTG5582IQSQSQL7249132.832604AAAATAGAAAGCGGAACCATA5583KIESGTI7250132.825605ACAACTCTTAGCCAACAAAGC5584TTLSQQS7251132.567606TTTCAGTTGGCTAGTAATCCG5585FQLASNP7252132.4465607TGGATTTCTACTGAGATGAGG5586WISTEMR7253132.356608GCCATAACAATCACTCAAAAA5587AITITQK7254132.1895609GTTACTGGTGTTGATTATGCG5588VTGVDYA7255131.7275610ATAATAGCATCCTCTACCACG5589IIASSTT7256131.506611ATTTATACGAATAGTCATGTT5590IYTNSHV7257131.43612AACGACATCCCCACACGAGCC5591NDIPTRA7258131.424613GGCGTAACCAACGCTTCCAAA5592GVTNASK7259131.404614AGGGGTAACACTCTCGAAATG5593RGNTLEM7260131.381615GGTATTAATCATGTGGCGTCT5594GINHVAS7261131.36616TTCAACGAAACTGCCGGGCGA5595FNETAGR7262131.2915617GCCTCGCAATCAGAAAAAAAC5596ASQSEKN7263131.243618GAACTTAACGAAAGGAACCTC5597ELNERNL7264131.06619GGAGAACAAAGCCACAACCAA5598GEQSHNQ7265130.951620TTGACTAATGATAATAAGTTG5599LTNDNKL7266130.846621TCTTATGGGCAGGGTCTGGAG5600SYGQGLE7267130.8108622CACAGTGACATGGGCTCAAGC5601HSDMGSS7268130.758623GCGTTAAAATCCGACAGCGCC5602ALKSDSA7269130.684624ACGAATCTTTCTCCTAAGACG5603TNLSPKT7270130.64725625GCTGATACGAATATTATTGTG5604ADTNIIV7271130.47626AGTGAGGGTAGTTCGCGGTCG5605SEGSSRS7272130.30865627AACTCTAGTAACACTGGTTGG5606NSSNTGW7273130.26628GTAACGAACGAATCCCGCGCC5607VTNESRA7274130.2145629GGGCGGCACACATTAGCGGAC5608GRHTLAD7275130.1035630GCTGTTGTGAATGTTGCGCAG5609AVVNVAQ7276130.094631AAAAAACCACAACAGTGACTA5610KKPQQ*L7277130.08632GGCAACGCTTCCGGAAACCCA5611GNASGNP7278129.97633TTTGCGGCTGGGGCGCATGGT5612FAAGAHG7279129.69634GGAGGAAACCAAAACCTTACT5613GGNQNLT7280129.6198635CATACGCAGTCGACGGGTTAT5614HTQSTGY7281129.541636CTATTGGGAAACGCACCCACA5615LLGNAPT7282129.534637GAGAAGGGGAATAGTGGGGTT5616EKGNSGV7283129.5155638GGCACGGAACCGCGCACTGCA5617GTEPRTA7284129.37639ATGCATGCGCAGGAGTCTCGT5618MHAQESR7285129.14615640CTGATTTCGACTGGTAATAAT5619LISTGNN7286129.021641AAGAATAATAATTCTGATTCT5620KNNNSDS7287128.767642GGGACATTAGCCTCAATGTCC5621GTLASMS7288128.734643AGGATTGATACGTTGTTGGTG5622RIDTLLV7289128.385644ATTTCGGGGTCTCATTTGAAT5623ISGSHLN7290128.3305645ACGGTTGAGGGTTCTTATCCG5624TVEGSYP7291128.288646ACGGAGTATCTGGCTGGTCTG5625TEYLAGL7292128.224647TATCTGGAGGGTGCTCATCGT5626YLEGAHR7293128.166648TTATCCGCAACATCTACGATG5627LSATSTM7294128.1455649ATGCTTAGTCAGGTTCTGACG5628MLSQVLT7295128.142650GCCAGGAACGTAATGCTGGGG5629ARNVMLG7296128.128651CTTCATGGGAATTTTAGTCAG5630LHGNFSQ7297128.112652GGCCACGGAAGTGACTTGACC5631GHGSDLT7298128.0576653GGTGTGAATTATCATACTACG5632GVNYHTT7299127.702654TATCTGCAGACGGGTACTCTG5633YLQTGTL7300127.624655GTAAACGGGGGAAAACCAGTC5634VNGGKPV7301127.5325656GAAGTAGGTAAAACCACCCAC5635EVGKTTH7302127.5065657CGACCCCCGAACGAAAACAGA5636RPPNENR7303127.49235658GTGGATAAGAATCATCCTTTG5637VDKNHPL7304127.431659AGTAAGTCGACTGAGATTATG5638SKSTEIM7305127.281660ACCGCTCTTCTATCTAACTTA5639TALLSNL7306127.228661ATGCACACAAGTAGACCCCCA5640MHTSRPP7307126.861662ACTCCAACTAACGGGAACCCT5641TPTNGNP7308126.785663ACGACGTCTGTGGAGAAGACT5642TTSVEKT7309126.7725664CAATACGACGCCAGCCGACAA5643QYDASRQ7310126.66665TACAACGCCCACGAATCATTC5644YNAHESF7311126.521666GACAACCAACAAGCCCTAGCT5645DNQQALA7312126.49667ACGAAGAGTTTTAATGATCTT5646TKSFNDL7313126.488668TTAGCCGACTCAAACAGCAAA5647LADSNSK7314126.48669CCGAGTACTCATGGGTATGTT5648PSTHGYV7315126.4775670CAGGTTCAGGGGACTCTGGGG5649QVQGTLG7316126.4394671CTGACTGCTGTTGCGATTAGT5650LTAVAIS7317126.235672AGGTATGAGAGTACTAGTGCT5651RYESTSA7318126.21673GCGGATCATAATCATATTGCT5652ADHNHIA7319126.21674TGGAATGCTGAGAATAGTAAG5653WNAENSK7320126.112675AACTCTGTCGTAGGGAACATC5654NSVVGNI7321126.111676TTCGGAGCAACCACCACAGCA5655FGATTTA7322126.048677GCTTCAGGGTCTGAAATGCCT5656ASGSEMF7323125.971678GACGGAACAAAAAGCGGAATG5657DGTKSGM7324125.871679TACACCGCCGACAAAAAACAA5658YTADKKQ7325125.562680CCGATTGCTGAGAGGCCTTCT5659PIAERPS7326125.558681AGCAACTCGTACTTACTCAAC5660SNSYLLN7327125.52682ACGAGAGAATTGACAAAAAAC5661TRELTKN7328125.47683CTCGGAAACCACTACACACCC5662LGNHYTP7329125.444684TTGCTCCAATCCATAGTGGTA5663LLQSIVV7330125.441685ATGATGGCGAATAATATGCAG5664MMANNMQ7331125.38686GGCGCGGACACCTCGACCCGG5665GADTSTR7332125.369687GGGTTCGGGCACGTGCCCGAA5666GFGHVPE7333125.324688AACGTTATGCACTCTTCCTCC5667NVMHSSS7334125.313689TCTGCGTCGAAAGTGGAATAC5668SASKVEY7335125.2945690ATTTCGAGTTATGATGGTAAT5669ISSYDGN7336125.273691AAAAAAACGAAAACACTAACT5670KKTKTLT7337125.26692GGTACCATATTACCAAACCAA5671GTILPNQ7338125.236693TTAAACGTCGTACCAACACAA5672LNVVPTQ7339125.09694AGTAGTGTTACTTCGAGGGAG5673SSVTSRE7340124.987695CCCATCAACGTACTCACGACA5674PINVLTT7341124.911696GGGGATAAGGCGAGTTTGGCG5675GDKASLA7342124.8255697AGGATGTCGGAGAGTTCTGAT5676RMSESSD7343124.5625698AATCTTTTGACTTCGTCGCCT5677NLLTSSP7344124.54699TCGCGGCTATCACAAGACCCC5678SRLSQDP7345124.3495700TGGTCGAATGCTCAGAGTCCG5679WSNAQSP7346124.231701GGCAGACACCTTCAATCGGAC5680GRHLQSD7347124.19702ATGAGTCTCGCCTCCACCCAA5681MSLASTQ7348124.092703ATGAGTACGGTTCTTCGCGAG5682MSTVLRE7349124.05704TCTAAATCTGAAAACCTGCAA5683SKSENLQ7350124.043705TGGACGGAAGGGGGCTCAGGA5684WTEGGSG7351124706TCGACTACGGTTTGGACTGCT5685STTVWTA7352123.99707GTTAGTTTGGAGAGTCGGTTG5686VSLESRL7353123.799708TCTATGTATGGGCAGGCTGGG5687SMYGQAG7354123.777709ACTAATACGCAGAATAATCCG5688TNTQNNP7355123.702710GTCGGTGACAGGAACTTGGTC5689VGDRNLV7356123.663711CTCGCCCACAACTACTTAAGC5690LAHNYLS7357123.6175712TGGACAGCTAACCAAGGCTTA5691WTANQGL7358123.566713GTCTTCCGGGAAGGCATCGTG5692VFREGIV7359123.54714CAGGTGCAGCATGAGAGGGTG5693QVQHERV7360123.5715CAAATATTAAACTACTCAGTC5694QILNYSV7361123.4716AGTACGATTGGTAATTCTACT5695STIGNST7362123.3029717CCTATACACCACGGTTCATCC5696PIHHGSS7363123.09718ATTGCTACTAATGTGATTTAT5697IATNVIY7364123.055719CAAGGCGGTACAAACAACCCC5698QGGTNNP7365123.037720ACCCGTGGCAACGACATATCA5699TRGNDIS7366123.023721CAAACGCTCATAGTGGGGTCC5700QTLIVGS7367123.007722CGGGGTCTGCCTGATGTTAAT5701RGLPDVN7368122.952723CTTAATGTGAATACGCTTAAT5702LNVNTLN7369122.896724GGGACAAAAAGCTGGCCTGTC5703GTKSWPV7370122.8432725ACGCATCTTGTGAGTGATTCG5704THLVSDS7371122.78726TGGACGGGCGCACAACCTTCT5705WTGAQPS7372122.73955727TCTGCGATGCACACATTAGTC5706SAMHTLV7373122.5735728TCCCAACACCACACGCCACTG5707SQHHTPL7374122.4691729GATAATCGGATGGAGGCTACG5708DNRMEAT7375122.416730TTGGGAGGAACCCTGGGAATA5709LGGTLGI7376122.38731TTTCATAATGAGTCTTATGGG5710FHNESYG7377122.36732ATTCGGACTTCTGTGATTAAT5711IRTSVIN7378122.333733TATAATACTGTTGATCAGCGG5712YNTVDQR7379122.2905734GCGCACCAAACCGCCGGGCCA5713AHQTAGP7380122.22735CCTCCGGAAAGTGCCAGGGGC5714PPESARG7381122.2044736AATAATACTTTGAATATTTTG5715NNTLNIL7382122.18737GCTAGTTATAGTAGTATGGTG5716ASYSSMV7383122.0975738TCGGGTCAAAACGGTACATCA5717SGQNGTS7384122.017739TTGTCTAGTATGAGTACGGAT5718LSSMSTD7385121.935740GTCGCCTCGATGGTACACAAC5719VASMVHN7386121.8215741ACGCAATTGTCAGACGGCTGC5720TQLSDGC7387121.81742GCGATTGTGGATAGGGGGAGT5721AIVDRGS7388121.757743AACCGTCAAAGGGACTTCGAA5722NRQRDFE7389121.734744GCACACCAAAAAGACATACGC5723AHQKDIR7390121.7745TTCACCGAACGCGCACTCCAA5724FTERALQ7391121.6915746ATGCTGTCTCATGGTGCGCTT5725MLSHGAL7392121.682747TCCGTAACCAACGGAGCGGAA5726SVTNGAE7393121.549748ATCACCGCCGCGTCACCGCAA5727ITAASPQ7394121.5325749CAAAACACGCAACGATACTTG5728QNTQRYL7395121.5036750ACTGGCCAAGGATTCTCGGCA5729TGQGFSA7396121.45751AGTTTTGAGAAGAATGGTATT5730SFEKNGI7397121.45752CTCACGTCCCACTCTGCGGGC5731LTSHSAG7398121.378753TCTACAATCGGCAACAGCACG5732STIGNST7399121.27754GGTCTTAGTCGGAATGATGGT5733GLSRNDG7400121.2415755TCGACGACGCACCCTTCCGAA5734STTHPSE7401121.238756CCAAGTACGAACGAAAGCCGC5735PSTNESR7402121.099757GGTACGAAGGATATTCTGATT5736GTKDILI7403121.039758TCTACTATTAATATGCGTGCG5737STINMRA7404120.929759TATATTGCTGGGGGGGAGCAG5738YIAGGEQ7405120.9760TCCAGCGGCCAACCGCTCGTC5739SSGQPLV7406120.7415761GACAAACAACAAACCGGACAA5740DKQQTGQ7407120.6775762GGGCTAGGACAACCCCAACTC5741GLGQPQL7408120.644763AGTCCGCAGCATGGTGTTATT5742SPQHGVI7409120.6145764TATAGGGGTAGGGAGGATTGG5743YRGREDW7410120.58765GCGGGGGGTTTGCTGTCGCGG5744AGGLLSR7411120.552766CCGATACAACAAGCCTCATTG5745PIQQASL7412120.375767TGGAGCGCCGGCGAACGGGTG5746WSAGERV7413120.3415768AGGGGTGATGTTGCTACGACG5747RGDVATT7414120.26769TTAACGGGACAAAACGAATTC5748LTGQNEF7415120.24770ACGACGCCGCCTTTTTCTAAT5749TTPPFSN7416120.2205771ACGAGTATTGGTAGTGCTAAG5750TSIGSAK7417120.195772AATGTGCAGAATGTGCCTGGG5751NVQNVPG7418120.16215773TATACGGGTACTCTTGTTGTT5752YTGTLVV7419120.047774GGAACCCACGCCTCAGCATAC5753GTHASAY7420119.959775CTGGTTGTTTCGAATAGTCTG5754LVVSNSL7421119.934776ACGCATCTTGTGAGGGATTCG5755THLVRDS7422119.7893777AATCATGGTCGTGCTATTGAT5756NHGRAID7423119.776778CCCAAAACTCTAACTTCGACA5757PKTLTST7424119.754779TTCGGTATAGGGCACGGAACA5758FGIGHGT7425119.734780GCGCTTCCGTCTCGTGAGCGG5759ALPSRER7426119.7235781GCGACTAGGGGTGAGTCGTCT5760ATRGESS7427119.715782GGGACAACCGAAGTTAACAAA5761GTTEVNK7428119.685783ACCCACACCCTTGGGGGAACA5762THTLGGT7429119.68784GAAGCAGTAACAAGTAAATGG5763EAVTSKW7430119.6575785CACTACGGTAACAAAGACATA5764HYGNKDI7431119.643786ATTTCTACGCATACGATGACG5765ISTHTMT7432119.64787GATACGTATAATAGTAATACT5766DTYNSNT7433119.6788GTTTTTACTGGGCAGACGGAG5767VFTGQTE7434119.544789TCGGTCACCAGTGGAACACAA5768SVTSGTQ7435119.502790CATACGTATTCGCAGGCTGAT5769HTYSQAD7436119.47455791GTAGCGGGCTTAGTCGACATA5770VAGLVDI7437119.41792GACTCTACCAAAGCCATGCAA5771DSTKAMQ7438119.403793GAGGGGCATAATCGTGGTATT5772EGHNRGI7439119.354794GGGTTGCATGGGACGAGTAAT5773GLHGTSN7440119.343795CCGCTTTCTCTTCATAATAGT5774PLSLHNS7441119.312796GCGAGTGATAAGGGGGCGAAT5775ASDKGAN7442119.249797GTGCTGTTGCAGAATTCTCAT5776VLLQNSH7443119.2225798CTATACGACGGAAAACACGTC5777LYDGKHV7444119.20995799ACCCAAGGATCTAACACCACA5778TQGSNTT7445119.08800TTCCTCGACAAATACAACTAC5779FLDKYNY7446119.058801GACACCGGAATCAAAAACGTT5780DTGIKNV7447119.05802TCCGGAGCGGCACAAAACCCA5781SGAAQNP7448119.019803ACCCTCCACACCAAAGACCTA5782TLHTKDL7449118.854804GCTACTTACGTTGTCGGAACA5783ATYVVGT7450118.84805CTTGTGGGGACTTTGGTGTAT5784LVGTLVY7451118.809806TCTAATACGACTGTGCAGCTT5785SNTTVQL7452118.76807AAGGCTCAGATTAATCAGATG5786KAQINQM7453118.727808CGGAATGCTACTGTGACTGTT5787RNATVTV7454118.655809GCAACCAGAGTGGGCAACCAC5788ATRVGNH7455118.599810AGTTATCAGAATCCTCCGCCT5789SYQNPPP7456118.512811TTTGATAGTTATAATATTGTG5790FDSYNIV7457118.51812GCTACTCTTTCTCCGCATGCT5791ATLSPHA7458118.497813TGGGAGAGTCCGACTAATGCG5792WESPTNA7459118.49814ATCGAAAACGTAAACCACTTG5793IENVNHL7460118.42815TATCGGGCTTCGGATGTGGCG5794YRASDVA7461118.372816CATATGTCTTCTGTTGCGACT5795HMSSVAT7462118.34817ATCCAAAGAGACGTGGGCCAC5796IQRDVGH7463118.2825818GAGAGTGTTAGGGAGACTATT5797ESVRETI7464118.25819CAGGGGGGGAATAGTCGGTTT5798QGGNSRF7465118.236820GAAAAAGGCACACCAAGTAGC5799EKGTPSS7466118.233821CACGACAGCACAACCCGCCCA5800HDSTTRP7467118.225822TTACCAACAGGCGTCCTGCCC5801LPTGVLP7468118.2065823ACCCTAGGCTACCCAGACAAA5802TLGYPDK7469118.1855824GCTAACACCGTCACAGAACGA5803ANTVTER7470118.17415825CACGACAAATCTATCCAACCA5804HDKSIQP7471118.16826GGAGGAACAGCCCTTGGGAGC5805GGTALGS7472118.123827GGGGGTAACTACCACACCACT5806GGNYHTT7473118.046828ATCTCAGAAATGACTAGGTAC5807ISEMTRY7474118.041829GTTGAATCTAAATCCGAACCA5808VESKSEP7475118.026830GACCGTGCCCAAAACAACGAA5809DRAQNNE7476118.006831ACGGCGCAGACCGGCTGGGTT5810TAQTGWV7477117.96832GGGTTCGGGCACCTGCCCGAA5811GFGHLPE7478117.86833CCTATTACGGGTTTTAGTGTT5812PITGFSV7479117.828834GATAGGACGTATTCGAATACG5813DRTYSNT7480117.7875835ATGTCAAACGCCTCCTACATA5814MSNASYI7481117.743836GATAATAGTAGGCCTGAGGTG5815DNSRPEV7482117.658837TCAAGTTCCCAAACGGTTTTG5816SSSQTVL7483117.655838AGTAATCTTGATGGTACTATT5817SNLDGTI7484117.643839AGTAATATGCGTGAGGAGATT5818SNMREEI7485117.629840AGACTTACAGAACTGGTCATA5819RLTELVI7486117.583841CAGGTTAGTCTGGTGAAGTTG5820QVSLVKL7487117.558842GAAATACACACGACCACAGGC5821EIHTTTG7488117.5505843AGCAGGATAGAAAACAACAAC5822SRIENNN7489117.5425844GGAACAGGCAAAGAAGTTCGA5823GTGKEVR7490117.521845TGGCAGGATCATAATAAGGTG5824WQDHNKV7491117.476846TCGACAAACTCTATAGGCGCC5825STNSIGA7492117.414847TCCGAATTAATGGTCAGACCC5826SELMVRP7493117.3623848CCGCTTCAGAATAATAAGACG5827PLQNNKT7494117.2175849CCTTATGCGAATAGGCTTGAG5828PYANRLE7495117.21145850GGGACGGTTTCGCTTATTCCT5829GTVSLIP7496117.175851GATGTTTATCTTAAGAGTCCG5830DVYLKSP7497117.1435852TTGCCGGATAAGGGGCGGATT5831LPDKGRI7498117.116853TCGATAACGACCGTAGCGAAC5832SITTVAN7499117.112854CCGCTTCAATCCCAATCGGGA5833PLQSQSG7500117.1045855AATAATATGGGTCATGGTCAT5834NNMGHGH7501117.0365856AGCGGACAAAAAAACTCAGAA5835SGQKNSE7502116.9665857ACCGAAGCGGGCCGCCCCCAA5836TEAGRPQ7503116.907858ACCTTACACACGAAAGACTTG5837TLHTKDL7504116.879859CTTCGAGACCTAAACGGAGGA5838LRDLNGG7505116.8691860GTTTGTGTTACTACTTGTGCT5839VCVTTCA7506116.861861GTCACAGCTGCTCAACCCCAA5840VTAAQPQ7507116.79862GCGACTTTTAGTCATGCTGGT5841ATFSHAG7508116.788863ACTTATGCGCCTAGGTCGCCT5842TYAPRSP7509116.75715864ACGTCGGAGATGCGTACTGCT5843TSEMRTA7510116.5885865TACTCGACAACCATGCTTAAC5844YSTTMLN7511116.584866TCTTTCACGAACACAAACCCA5845SFTNTNP7512116.5665867AGTCCTCCTAGTACGTCGGGT5846SPPSTSG7513116.551868GTGACGACTGTTGATAGTGCT5847VTTVDSA7514116.477869GAGGCGCATAATCGTGTTATT5848EAHNRVI7515116.461870ATGGAGTTGACTTCTACTAGT5849MELTSTS7516116.456871CATTTGGTTACTAGTGGTATT5850HLVTSGI7517116.45872CAAACCATCACCTCACAAATG5851QTITSQM7518116.431873ACTGCGAATAGTACGTATGTG5852TANSTYV7519116.329874CTTATCCAATTATCGGGTCAA5853LIQLSGQ7520116.317875TCTTACGTTAGCGTCCCCGCC5854SYVSVPA7521116.3005876GTGCATGGGAATGCTCCGGCT5855VHGNAPA7522116.2665877GCCGGAAAAACCCACGCCGAC5856AGKTHAD7523116.228878ACATTCCACCAAGGGGTCAAA5857TFHQGVK7524116.175879TTAGGAAACAACCGGCCACTA5858LGNNRPL7525116.17880CTGCACCTCGTCCGGAGCTTC5859LHLVRSF7526116.08881TCCTACAGTACTTCAACACCG5860SYSTSTP7527116.036882ATATCGCAAGGCTCGAGCCTC5861ISQGSSL7528116.025883CTCCAACTGGCTACATCCCAC5862LQLATSH7529116.0035884GTGACTCAGCGGTTTGCTGAG5863VTQRFAE7530115.952885GCTATAGACTCCATCAAAATG5864AIDSIKM7531115.9415886GACGCACACACTTTCAGCCGG5865DAHTFSR7532115.93887CGTGGTTCAGACGGAGGATTG5866RGSDGGL7533115.911888TTAGCACAAGGCACGGACCGG5867LAQGTDR7534115.884889AAAAACAACAACTCAGACAGT5868KNNNSDS7535115.7595890GAAAACGAAAAACGAGAAAGC5869ENEKRES7536115.741891AACGAACAATTCGAAAAAGTC5870NEQFEKV7537115.705892ACACAAGTAGTCGCAAGAACA5871TQVVART7538115.68045893GGAGTAAACGTCACCAACAGC5872GVNVTNS7539115.64894GCCGACAAAGGATTCGGCCAC5873ADKGFGH7540115.5886895ACTCATAAGCAGGTGGATCTT5874THKQVDL7541115.54825896TCGGCTAACTTATACAAACAA5875SANLYKQ7542115.544897AAGCTGCATACTAAGGATCTT5876KLHTKDL7543115.54898GTGGTGGTTCACACTATCCCA5877VVVHTIP7544115.52899TCTACGTCTCAGGCTGTGCAG5878STSQAVQ7545115.496900CGTAACGGCTCCGCCCAAAGC5879RNGSAQS7546115.465901CATTATGGGAATAAGGATATT5880HYGNKDI7547115.402902AGCTTCTTGGTAGCCCACCCA5881SFLVAHP7548115.4903CAGCAGAATACGAGTTTGCCG5882QQNTSLP7549115.39904ATGCACGTCGACAAAACGAGT5883MHVDKTS7550115.379905AATAATGAGAATACGCGTAAT5884NNENTRN7551115.363906TCGATAAACAACATAGGCGCA5885SINNIGA7552115.3425907GCTACTATATCGGACCGAGCC5886ATISDRA7553115.327908TACTCAAACCTCGTACTTTCC5887YSNLVLS7554115.285909ATGATGAATGTGAGTGGTCAT5888MMNVSGH7555115.2555910GGGGAGACGCGGTCGACTGCT5889GETRSTA7556115.18911ACGAAGGGTTATAATGATCTT5890TKGYNDL7557115.1635912GCGTATAATATGTCGTCTGTT5891AYNMSSV7558115.148913GCAGACCCCGCTAAAGGCAAA5892ADPAKGK7559115.1435914TATATTTCGGCGCCTCCGATG5893YISAPPM7560115.1145915CGAAACAACCCATCGCACGAC5894RNNPSHD7561115.069916GGAACCTCCATAGACTACGTA5895GTSIDYV7562115.053917GGCACCGGGTACCCAAACCAA5896GTGYPNQ7563115.038918GATCATATGAATTTGAGGTCT5897DHMNLRS7564114.9475919ATTAATTCGTATTTGCATGAG5898INSYLHE7565114.887920TGGCAAATGGGGGCCGGGAGC5899WQMGAGS7566114.833921ATGGGTATCGGGTCATACAAA5900MGIGSYK7567114.827922CAAAACCACAACGAACTAAAA5901QNHNELK7568114.749923GATAAGTCTAATTATAGTATT5902DKSNYSI7569114.736924ACAACGAAACCGGTCGCGGAA5903TTKPVAE7570114.7315925GTGACTGTGAGTAATAGTCTG5904VTVSNSL7571114.685926ACGGCGTATCTGGATGGTCTG5905TAYLDGL7572114.665927AATTTGCAGACTGGTGTTCAG5906NLQTGVQ7573114.65928ACCGTCGCTCCCTACAGTAGC5907TVAPYSS7574114.65929GTTCAGATTTCTATGAATAAT5908VQISMNN7575114.617930TACATAGCAGGTGGTGAACAA5909YIAGGEQ7576114.60015931TTCATGGAAGTCATGAAAAAC5910FMEVMKN7577114.547932ACGACTGATAAGGGTATTAAT5911TTDKGIN7578114.539933TTGAGCTACAGCATCCAACAC5912LSYSIQH7579114.53934GCTTATAATGCTCGTCTGCCT5913AYNARLP7580114.49305935AACACCGGCACCACGAGTGTC5914NTGTTSV7581114.475936GTGCTGAGTACGGGGCTGCGG5915VLSTGLR7582114.4165937AACGACTCCTCGTCAATGTCC5916NDSSSMS7583114.397938CGCCAAGGCAGCTTGATGATA5917RQGSLMI7584114.37939ATCAGCACCGCATACATGTTG5918ISTAYML7585114.36940GGTACTATGAATATTGGTATT5919GTMNIGI7586114.356941CATAATAATAATTTGCTGAAT5920HNNNLLN7587114.292942CATTTTTCGCAGATTACTAAT5921HFSQITN7588114.278943GACCTGACCAGAGCTGCAATA5922DLTRAAI7589114.256944GTCGCTATGGGAGGCGGTCCC5923VAMGGGP7590114.1845945GCCTACGGTATCAGAGAAGTG5924AYGIREV7591114.1465946ACATCAGACGGTCTACTAAGT5925TSDGLLS7592114.128947ACGATGGCTACAAACTTAAGT5926TMATNLS7593114.082948AACAACGGCAACTCATCAAGG5927NNGNSSR7594114.047949ACGGAGAAGGCGAGTCCTCTG5928TEKASPL7595114.031950CTCAACCACACAATGCCCCTC5929LNHTMPL7596114.027951GATACGGCGAGTTATAATAAT5930DTASYNN7597114952AACATGACCAACGAACGGCTC5931NMTNERL7598113.9675953GTAGTCTCATCGGGCGGCTGG5932VVSSGGW7599113.966954GTGAATCAGAGTCCTGGGGCT5933VNQSPGA7600113.85955GATCATCATCCTCAGAGTCGT5934DHRPQSR7601113.83956CGATGGCAAGGACTGAGCGCG5935RWQGLSA7602113.76957GCGGTTACGACAAGCGTGAGG5936AVTTSVR7603113.752958TGGGGAGTCAGTAACTCAGCA5937WGVSNSA7604113.7505959GCGCATATGCATTCGGAGTTG5938AHMHSEL7605113.74960AATAATCTTACGAATTCGACG5939NNLTNST7606113.736961AGTAGTGGGGGTATGAAGGCG5940SSGGMKA7607113.69962GTTGGGTATGGGGAGCATGTT5941VGYGEHV7608113.64963ACCATAGTGTCCACTTCTTAC5942TIVSTSY7609113.628964CCCACCAGTCACCAAGAACCC5943PTSHQEP7610113.62965TCTAACCTTCGAAACACAATA5944SNLRNTI7611113.58966TCAAGACACGACGTCCGAAAC5945SRHDVRN7612113.559967CAGATGAATATTCATGATAAG5946QMNIHDK7613113.543968TGGGCTATGAATAATGTGCCG5947WAMNNVP7614113.531969GCGATGGATGGGTATAGGGTT5948AMDGYRV7615113.462970AAAGGGGGAAACCTCACCGCA5949KGGNLTA7616113.4525971ATTGGTAAGGATAGTGTTCCG5950IGKDSVP7617113.448972GTGCAGTTGACGCATAATGGG5951VQLTHNG7618113.43973GGCCTGAACCAGATCACATCG5952GLNQITS7619113.4974AGGGGTGATCCTTCTACGCCT5953RGDPSTP7620113.4975GTTCCCTCCGACCCCCACTGG5954VPSDPHW7621113.35976ACGTTAAGTTCCCAAGTCACA5955TLSSQVT7622113.327977AACCAAAGAGTTGAACAAAAA5956NQRVEQK7623113.3075978GTACTTCCAAGTCGGATCGCG5957VLPSRIA7624113.3979GGGCACTACGCTACAAACACA5958GHYATNT7625113.212980CCTTCGATTCCGTCGTTTTCG5959PSIPSFS7626113.207981ACTTATGAGTATCCGACTCGG5960TYEYPTR7627113.19982AAAGACCACATCCTCAGCCTC5961KDHILSL7628113.1795983GGCACAGGAGGTAACCGAGAA5962GTGGNRE7629113.173984AAGGGGGATGGTGCTTATGAG5963KGDGAYE7630113.162985TCTTCTTTCGGAAAAGACAAC5964SSFGKDN7631113.1603986ACAGTATCGTCATACGTACAA5965TVSSYVQ7632113.0595987AGGGCTCATGGGGATAATCAG5966RAHGDNQ7633113.036988TATCATGCTCATAGTAATGAG5967YHAHSNE7634113.03989GCAAACTTGCCCAGCGGTCAC5968ANLPSGH7635113.03990GCGAACCTCAACTTGACCAGT5969ANLNLTS7636113.015991AGGCTTAATGCGGGTGAGCAT5970RLNAGEH7637113.0105992TATGTTGATTATAGTAAGTCG5971YVDYSKS7638112.9935993GCTAATTCTGGGTTGCATAAT5972ANSGLHN7639112.9695994ACGAGTGGTGTGCTTACGCGG5973TSGVLTR7640112.9485995GGAAAACCAGCACAAGAATTC5974GKPAQEF7641112.933996GTGGGGACGCATTTGCATTCG5975VGTHLHS7642112.918997CCGATGAACAAAGACATACTG5976PMNKDIL7643112.9116998GACGCCCACCACTCAAGCAGC5977DAHHSSS7644112.88999ACTAACGCCATCTCTCAAACG5978TNAISQT7645112.79971000GTTTTGTCTGATAAGGCGTAT5979VLSDKAY7646112.7871001AACCTACTTGTCGACCAACGT5980NLLVDQR7647112.781002ACTGGTCATCCGCCGGCGGCG5981TGHPPAA7648112.77351003ATTAGTTCGGGGATTTTGTCG5982ISSGILS7649112.72051004AATACGAATTTGTTGGGTTAT5983NTNLLGY7650112.721005ACGCTATCGGTTACCCTGGGT5984TLSVTLG7651112.711006CATACTGGTGTTCAGACTAAT5985HTGVQTN7652112.7041007GAGGTTAGTAATAATAATTAT5986EVSNNNY7653112.691008CTGGCTAATATTTCGCTGTAT5987LANISLY7654112.691009GTGGAGCATGTTGCTCATCAG5988VEHVAHQ7655112.6561010GTCGACAAAAGCGAAGCCGAC5989VDKSEAD7656112.61011GGCTTCGCATTAACTGGCACC5990GFALTGT7657112.5641012TTGTTGACGGCTCCGCATAGG5991LLTAPHR7658112.531013AATGCGGGGGCTCTTATGGGT5992NAGALMG7659112.5181014AGGACGCAAGCAGGGGACTCA5993RTQAGDS7660112.4831015AACACACACAGACAAGAATAC5994NTHRQEY7661112.4611016AACATAGCAGGCGGAGAACAA5995NIAGGEQ7662112.4421017GAGATTAATAATCGGACTGGT5996EINNRTG7663112.432351018ACCGTTAACACAATGTACACG5997TVNTMYT7664112.41019CCTATGAATGGTATTCTGTTG5998PMNGILL7665112.3881020AATCCTAGTTATGATCATCGG5999NPSYDHR7666112.3631021GCTGTTATTCTGAATCCTGTT6000AVILNPV7667112.361022CTGTACGGGGGAGCACACCAA6001LYGGAHQ7668112.34551023CAAGTCAACCAACCGAGAATA6002QVNQPRI7669112.331024GCTGTTAGAACACCGGCAATG6003AVRTPAM7670112.3261025AGTTTGACGCCTAATAATCTT6004SLTPNNL7671112.2831026CTTGGGCAGGTTAATTCTACG6005LGQVNST7672112.2051027GCTAATTCTGCTACTAATCAG6006ANSATNQ7673112.16051028TCCTTGACGGAAAAAGCGCCG6007SLTEKAP7674112.151029CAATTCCACGGGACATCTGAA6008QFHGTSE7675112.1251030AAAAACGGCGCCATAGGAACA6009KNGAIGT7676112.08671031GTGCTGGCGTCGACTGAGAAG6010VLASTEK7677112.0581032AGTAATATGAGTGAGGCGATT6011SNMSEAI7678112.021033AACGCTAACGCCGGTGGAAAC6012NANAGGN7679112.01481034CACTCTAACACACACTACGAA6013HSNTHYE7680112.0051035AGTGCTTTGATTAGTGTGGTT6014SALISVV7681111.9931036GTGGCGACTCATTATAATGAG6015VATHYNE7682111.9711037AACCAAACGTTACAAGTAGAC6016NQTLQVD7683111.971038AAAACACCCTCAGCTTCAGAA6017KTPSASE7684111.9571039GGTGAATCACGTACAAACATG6018GESRTNM7685111.93931040CGGAATGAGCCGGTTAGTACT6019RNEPVST7686111.9121041GCAACACACGCCATGCGCCCA6020ATHAMRP7687111.90051042TGGGAATCCCTCTCCAACGCA6021WESLSNA7688111.8851043CATAGTCCTCCTACGACTATG6022HSPPTTM7689111.8471044TCTACCATGAACACGATCACG6023STMNTIT7690111.81621045AACATGGAACACACCATGGCG6024NMEHTMA7691111.789651046CATAATACGGAGTCTAAGACT6025HNTESKT7692111.7781047CACAACTTAATGACCCAAATA6026HNLMTQI7693111.771048AACCAAAACACCTACGAACTG6027NQNTYEL7694111.7561049TACGCCACTCTCGACACCATC6028YATLDTI7695111.7521050GTTCAGTTGGAGAATGCGAAT6029VQLENAN7696111.72151051GGGCTCACAGGATACACAATG6030GLTGYTM7697111.711052TTAGTACTTGACTCACGGAAC6031LVLDSRN7698111.7041053ATGTTGGTACAAAACACACCC6032MLVQNTP7699111.7021054CCTCATAATCAGGAGATGGGT6033PHNQEMG7700111.68651055TCGTTGGGGGATGCGATGTTG6034SLGDAML7701111.67761056CGCGCCGAAGGGAGCTCTGGC6035RAEGSSG7702111.66451057AGTGAGGAGAGGACGCGTGCG6036SEERTRA7703111.6161058TCTAGTAAGGAGCGTACATCG6037SSKERTS7704111.571059CCTGTTGTGAGGGATCGTTCT6038PVVRDRS7705111.56431060AGGATGTCTGAGAGTTCGGAT6039RMSESSD7706111.511061AACCAATCTATAAGCATGGAC6040NQSISMD7707111.4911062GTCGCTGTATCGAACACTCCA6041VAVSNTP7708111.4821063GGAGACATCTCAAGCAGAAAC6042GDISSRN7709111.46031064GCTGCCGGAGCCGACTCTCCA6043AAGADSP7710111.4291065TTCGGCACATCGTACACAACC6044FGTSYTT7711111.4011066CGTGATACTAATACGGATAAG6045RDTNTDK7712111.3361067GGGTCTACGCCGGGGGCGAGT6046GSTPGAS7713111.3271068GGTACTAATCATGATTTTTCG6047GTNHDFS7714111.3021069AATGAGAGTACGAAGGAGAGT6048NESTKES7715111.28451070GTGCATGTGACTAATGTGTTG6049VHVTNVL7716111.22951071AGTACTACTAATGTTGCGTAT6050STTNVAY7717111.20151072ATTACGTCGTTGAATGGGATG6051ITSLNGM7718111.16151073GAAGTACGGGGCAGCGTGCCA6052EVRGSVP7719111.14351074GCACTTACCCGTATGCCTAAC6053ALTRMPN7720111.12351075CTCAGTGTAGCCGACAGGCCA6054LSVADRP7721111.061076GTTTCTACGGCGCAGAGGCAG6055VSTAQRQ7722111.0561077TTAAACGCAGAATACACCAAC6056LNAEYTN7723111.021078AATGAGAAGCCGCAGTCGACG6057NEKPQST7724111.0091079TTGAATACGCTGATTGATAAG6058LNTLIDK7725111.0031080GTCACACACACACTGATCGAA6059VTHTLIE7726110.9871081GAGCAGAAGAAGACTGATCAT6060EQKKTDH7727110.9361082ACATCAGGCATGTACGACACG6061TSGMYDT7728110.921083CCTGACGCAGCGCGTAGCCCG6062PDAARSP7729110.9161084TTGACGCAGGTTTATCATGAG6063LTQVYHE7730110.911085AGAGAAATGAGCAGCCTATCT6064REMSSLS7731110.8911086ATGCCTTCGAAAGGCGAAGTA6065MPSKGEV7732110.8161087AATGAGCAGAATACGCCGAGT6066NEQNTPS7733110.791088AAAAACTACGCAAGCACCGAC6067KNYASTD7734110.74351089TGTATGGATGTTGGTAAGGCG6068CMDVGKA7735110.7111090GCTCTTCATAATCTGATGAAT6069ALHNLMN7736110.7111091CCTGACAGAGCGAACGACAAA6070PDRANDK7737110.68351092ATTGCTCATGTGTCTACTAAT6071IAHVSTN7738110.68051093AACGGTCCGACCGGATCCGCC6072NGPTGSA7739110.66521094TCTACTCATCATGCTGATCGT6073STHHADR7740110.6291095GGTTCGCAGTATGGGCGGCAT6074GSQYGRH7741110.6291096ACCGGAACGGCTACACTCCCA6075TGTATLP7742110.58251097AAAGCCCACGTTGTAGAAATA6076KAHVVEI7743110.57951098ACTTCGCAGGGTAGGAGTCCT6077TSQGRSP7744110.5111099TTATCCTCCGAATCACCCAGG6078LSSESPR7745110.50151100ACCGGGGTTCGAGAAACCATA6079TGVRETI7746110.45751101ATGGATACTGAGCTTTATAGG6080MDTELYR7747110.44751102ACACCTGAAGCGAGCGCTCGC6081TPEASAR7748110.441103CACGACTTGAACCACGGAAAA6082HDLNHGK7749110.4281104CTTACTGGTCAGAATGCGATT6083LTGQNAI7750110.4161105ACCGTCGGATCGAACAGTATA6084TVGSNSI7751110.4111106CATACTGTGGGGGCTATGCAT6085HTVGAMH7752110.411107GAACGAGTCAACGGGATGGCA6086ERVNGMA7753110.4051108TCCGAACCCCTTAGAGTTGGA6087SEPLRVG7754110.37251109GTCTCTAACGTCCTCTACAGC6088VSNVLYS7755110.3461110TTCTCCTCCGGAACAACCATA6089FSSGTTI7756110.31111ACAAACCTAAGTCAATCGGCC6090TNLSQSA7757110.244351112CCTAATACTGCTAGTAATTTT6091PNTASNF7758110.22741113TGCGGCCTGAACTGCGGTAAA6092CGLNCGK7759110.2111114CCGACCGGAGGCTCACCACCA6093PTGGSPP7760110.2011115TACCTAGAATCCAACTACACC6094YLESNYT7761110.181116ACATTAGAAACAACCCGCAGC6095TLETTRS7762110.1671117TCCGCTAACGAACACAACCAC6096SANEHNH7763110.1371118GCACGAGTGGACACCAACCAA6097ARVDTNQ7764110.091119AACGTGGTGAAAAACAACACA6098NVVKNNT7765110.0771120GGTTCTTATTCTGATGGTAGT6099GSYSDGS7766110.03551121CCCGGTAACGGACAAAGTCCG6100PGNGQSP7767110.02751122TCGGGGGTAAACTTCGGAGTA6101SGVNFGV7768109.9981123CGAATCAACGCAGCAATCGAC6102RINAAID7769109.996751124CAAGCTGGGAACGCGCCAAGG6103QAGNAPR7770109.988251125CAGTCGGGGTCTCTGGTGCCG6104QSGSLVP7771109.9621126TTCTCAACGCAAGACATAAGC6105FSTQDIS7772109.9481127GTGAATCCGCATCCTGCGCAG6106VNPHPAQ7773109.9481128AAAGGCCACGCCTACGAAGCC6107KGHAYEA7774109.8971129GAAGACAGTATGAGATTCTCT6108EDSMRFS7775109.8741130GGTAGGAATGAGAGTCCGGAG6109GRNESPE7776109.8551131TCCGACGGATCGAAACTACTA6110SDGSKLL7777109.82051132ACTCTCTCAGGCTACATGAGA6111TLSGYMR7778109.8081133GATATTCATAATCCGCGTACG6112DIHNPRT7779109.7891134TGGGCCAAAGACGTCAACGTC6113WAKDVNV7780109.7821135GCTGTGGGGCGGTCGGATGAT6114AVGRSDD7781109.7111136AAAGAAAAAACCACCCGCGAA6115KEKTTRE7782109.6971137CTGCTCCAATCGACCTACTTG6116LLQSTYL7783109.6721138AAGTCTAATTTGGAGGGTAAG6117KSNLEGK7784109.62851139ACGAGGACGCCTTTTCTGGGG6118TRTPFLG7785109.6131140CAGTCGGATACGACTTCGATT6119QSDTTSI7786109.6051141GCGTGGTCTCAAGTCCTGACG6120AWSQVLT7787109.5871142ACTCAAGAACGACCACTAATC6121TQERPLI7788109.561143GATGATAAGACTGGTCGGTAT6122DDKTGRY7789109.5491144TTTCCTTCGCATAATGGGGCG6123FPSHNGA7790109.541145ATGCTGTCTCAAGTCTTAACA6124MLSQVLT7791109.5361146TCTGTGACGACTAATCTGATG6125SVTTNLM7792109.4841147GAACACAACTCAAAAACTTAC6126EHNSKTY7793109.47451148TATGCGCATCCTGTGACTCAT6127YAHPVTH7794109.46351149CCTAATCCGTCTCCGAGGCAG6128PNPSPRQ7795109.4491150CATATGGGTTTGAATGAGCTT6129HMGLNEL7796109.4271151AACAGTTTGCAAGCAAGTGCA6130NSLQASA7797109.4021152GACCTCGGTACGGCTAGAACC6131DLGTART7798109.3881153TACGACAGCCGACTCTACGCG6132YDSRLYA7799109.38531154CCGAAGCCTGGGACGGGGGAG6133PKPGTGE7800109.37211155AGTCTGAATGGGGTGTTGGTT6134SLNGVLV7801109.36851156CAGTCTAATTTGGTTATTAAT6135QSNLVIN7802109.3591157GCGTCTCCGGCGCAGACCGGC6136ASPAQTG7803109.3311158AACATGACCAACGAAAACGGA6137NMTNENG7804109.3241159TCACTTCGGACGGACGAATTC6138SLRTDEF7805109.318151160ATATTGGACAACCACCGTTTC6139ILDNHRF7806109.26851161TTGATTAATATGAGTCAGAAT6140LINMSQN7807109.2641162CCGCAAGACGTCCGCCAAACA6141PQDVRQT7808109.26251163CCCTTCGTAGCGAACGAACCA6142PFVANEP7809109.2561164AATATTAATGATACTAAGAAT6143NINDTKN7810109.2531165AATTTTAGTAGTGGTGATGTT6144NFSSGDV7811109.2291166GAACGAAACGGACTAATAGAA6145ERNGLIE7812109.2151167AATTCTCATGTTCCTAATAAT6146NSHVPNN7813109.21151168AACACAACCGGTAGCTCGGGC6147NTTGSSG7814109.19251169TCAACCAGAAAAGAACACGAC6148STRKEHD7815109.18751170GCTGCTAATCCTAGTACGGAG6149AANPSTE7816109.13571171TCGGGTATGAATAGTAATAAG6150SGMNSNK7817109.1291172AAGACGCTTGATAATAATGCT6151KTLDNNA7818109.093051173ACCGTAAAACAAACAAGTCCG6152TVKQTSP7819109.08631174ATTTCTCAGGTGTCTTTTAAT6153ISQVSFN7820109.0821175TTAGAAGTAAACCTGCAAACG6154LEVNLQT7821109.0571176GAAATGCAAACCAAAAACGCC6155EMQTKNA7822109.0521177GCCGACAACAGAAACGACAAA6156ADNRNDK7823109.0081178GCGTATGATACGCTGAATAGT6157AYDTLNS7824108.9821179ACGATTCAGGATCATATTAAG6158TIQDHIK7825108.9421180GACCCCACTAAAGTTGGATCC6159DPTKVGS7826108.9391181TCCCTCCAACGAACCCCCGAC6160SLQRTPD7827108.9371182GCAAACGACTCTGCCAAAACA6161ANDSAKT7828108.91251183AAAAAAGTCGAACAAGAACCA6162KKVEQEP7829108.9071184GCAAGTCGGGACCTGGGACAA6163ASRDLGQ7830108.9061185TGGGAGAGTGATAAGTTTCGT6164WESDKFR7831108.8761186AACCGCGGAACAGAAGTTTAC6165NRGTEVY7832108.81871187AATATTAGTAGTATTAATCAG6166NISSINQ7833108.81551188GCCTCGAAAGGCTTCGGCCAC6167ASKGFGH7834108.78861189CAGTCGCAGAATGTGACTCAG6168QSQNVTQ7835108.78251190AACGGATACCAACTACAAATC6169NGYQLQI7836108.7791191TGTACTAATGCGTCGGATCTT6170CTNASDL7837108.741192ACCGTCGCCTCGCCCAACACC6171TVASPNT7838108.7381193AATACTGCTCCGCCGAATCAT6172NTAPPNH7839108.7331194CTTTCTCAACAACGCGACTAC6173LSQQRDY7840108.692451195TGGAATCAGAATGTGTCTCAT6174WNQNVSH7841108.67851196ACAGGTAGTTCAGACAGATTA6175TGSSDRL7842108.6761197AACACAACGCCACCTAACCAC6176NTTPPNH7843108.6021198GTGGTCGACTCAACATACCCG6177VVDSTYP7844108.5921199ACGGATGCTACGGGGAGGCAT6178TDATGRH7845108.59051200TTGTTTACTGCTGGGAGTACT6179LFTAGST7846108.581201TTGCGTGATCAGACTAGTATG6180LRDQTSM7847108.5661202ATCGAAACGGACCGCCACCGG6181IETDRHR7848108.5311203AGTGGGCCTGAGAATACGTTG6182SGPENTL7849108.5261204GACAACCAAAACGCCGACAGG6183DNQNADR7850108.4861205CATGATGGTTATGTTCCTAAT6184HDGYVPN7851108.4691206CATATGTCTAGTTATTCGTCG6185HMSSYSS7852108.4361207AGTCGTCTGCAGACTCAGCAG6186SRLQTQQ7853108.43581208TCATACACAGCAGGAAGACCC6187SYTAGRP7854108.4171209GTGCAGCAGAATAATATTAAT6188VQQNNIN7855108.3761210GATGCGAAGGCTCTTACGACT6189DAKALTT7856108.3681211AAGGATGAGCATCTTCATTAT6190KDEHLHY7857108.3581212CACGGTGACCGAACAGCTTTA6191HGDRTAL7858108.3271213AATTTTACTATTACGGAGGCG6192NFTITEA7859108.321214GACACTCACATGAACAAACTG6193DTHMNKL7860108.3161215CAACCAGGAGCCCCCCAAACC6194QPGAPQT7861108.3121216GGGGAAGCACGCCGAGAAGCC6195GEARREA7862108.3021217AAGTCTCTTAGTAGTGATGAT6196KSLSSDD7863108.23751218ATGAATACGACTTATAATGAG6197MNTTYNE7864108.2311219GCGGCCGCACTAGAAACAATA6198AAALETI7865108.2231220AACGTCGCTCCCTACAGTAGC6199NVAPYSS7866108.215951221TCTGCGGGTATGGTGAGTCTG6200SAGMVSL7867108.21451222TGCGACTTGTCACAATCATGC6201CDLSQSC7868108.1331223GTTTTGATTACGATGAGTTCG6202VLITMSS7869108.1181224CAAGTTGGGGCTCTAATGGTT6203QVGALMV7870108.0371225CAACGTACCTCGGAAGCGCCA6204QRTSEAP7871108.03151226TTGGGTAATGGTAGTTCTTTG6205LGNGSSL7872108.01351227CCTAGTGTCCGTTTGCCCTTA6206PSVRLPL7873108.0071228GATTCTGCTCCGAGTACTATT6207DSAPSTI7874108.0031229AATTATAATGGGGTTAATGTG6208NYNGVNV7875107.9561230TCGGCTCATCAGACGCCGACG6209SAHQTPT7876107.9321231GATCATAGTAAGCAGATTTCG6210DHSKQIS7877107.9231232GCCGCCAGCTTGTCGCAAAGC6211AASLSQS7878107.9141233CACGCCGACGTTGGCATGAGC6212HADVGMS7879107.8881234CACGTGACAGTAACGTTAAAC6213HVTVTLN7880107.88651235AATTCTACGCATATTAATTCG6214NSTHINS7881107.88431236CTGGGGCTTGCTGGTCAGGTT6215LGLAGQV7882107.8841237AGCAGTCAAGCCCACGGCCCA6216SSQAHGP7883107.8721238GCTTTTAAGTCGGGTAGTATT6217AFKSGSI7884107.8661239CACTCCCCATCCCACGACTCG6218HSPSHDS7885107.8441240CCAAACGGCGAAAGTTCGCGA6219PNGESSR7886107.83031241ATTCTTACGCCTTTGGATAAG6220ILTPLDK7887107.8251242TCCGCCTCTTACTCCAGGATG6221SASYSRM7888107.8151243GAGGCGTTGCATGATCGGAAT6222EALHDRN7889107.7931244GGTGAACAACACAACGCCCCC6223GEQHNAP7890107.7781245GGGAATATGGTTACGCCTAAT6224GNMVTPN7891107.7531246AACGCTCTCCTCAACGCACCT6225NALLNAP7892107.7421247GCAAGTGACCTACAAATGACG6226ASDLQMT7893107.7231248TCGTATGATATGCATACGAAT6227SYDMHTN7894107.7051249AATATGTCGCATAGTACTCTG6228NMSHSTL7895107.67771250ACTGCCAACAACCACTCTCCG6229TANNHSP7896107.6711251CAAGCCCCGCCAACAGCACAA6230QAPPTAQ7897107.6681252AACTACCACGGAGACAACGTT6231NYHGDNV7898107.6371253AGGGATAGTACTATTAGTCGG6232RDSTISR7899107.6351254GTTTCTTCGCCTAATGGTACG6233VSSPNGT7900107.60951255TCCCGAATCACGGTGAACGCA6234SRITVNA7901107.5931256GTCGGAACAACCTCGAACGGC6235VGTTSNG7902107.5751257CATACGAATCAGATGCAGCCT6236HTNQMQP7903107.55731258AAAAGCAACGCGGGATTCGGT6237KSNAGFG7904107.50651259AAAGAAAGCCTCGAAGACGTC6238KESLEDV7905107.491260GCGCAGGTTAATAATCATGAT6239AQVNNHD7906107.4891261AACGCTTCTACCTACATGGAC6240NASTYMD7907107.4791262ACGTCTGATACGAATGCTAGG6241TSDTNAR7908107.46051263GAGAGTCGTATGCGTAGTATT6242ESRMRSI7909107.4511264CGTGTTGAAGACACCAACTCC6243RVEDTNS7910107.4161265GCCTCTAACCACCTACAAGCC6244ASNHLQA7911107.38631266CGCTTACACGGCTCAGACTCG6245RLHGSDS7912107.3581267ACCGTCGAACAAATAAACTCG6246TVEQINS7913107.3491268AGGTCCGTACCATCACCACAC6247RSVPSPH7914107.3431269GAATACCTCGCCCTGGGACAC6248EYLALGH7915107.3361270AATACTAATAATCAGGAGCAG6249NTNNQEQ7916107.3321271AACTACGGTTCCGGACGAATC6250NYGSGRI7917107.32051272CGCCACGGGGACACACCGATG6251RHGDTPM7918107.3031273AACGACACCATCGGCAGACCA6252NDTIGRP7919107.29951274TATGGGGAGCGTGCTAGGACG6253YGERART7920107.2971275GTTCTTGGGATGCAGAGGTCT6254VLGMQRS7921107.2951276CTTCATTTTCATGCTTCGCAG6255LHFHASQ7922107.2811277ACCGACACGCTCAGCGAAAGA6256TDTLSER7923107.2471278GGGACAGGTACCGTTGGATGG6257GTGTVGW7924107.2031279ACAGAAAGCCCCAAACTACTA6258TESPKLL7925107.20151280ACGATTAGGAGTGAGGGTTTT6259TIRSEGF7926107.14951281GCGTCTAGTTATATTAATAAT6260ASSYINN7927107.1441282TTACACCTTGGGTTATCATCT6261LHLGLSS7928107.14151283GTCACTGGCACTACCCCGGGA6262VTGTTPG7929107.1371284GTGACGTCGTCTGCTAGTGGT6263VTSSASG7930107.06061285CAAATGCACCTACACATGCAA6264QMHLHMQ7931107.0571286GGTACCATGAGTCTATTAATG6265GTMSLLM7932107.0461287TGCGCATCAGAAGTTTGCCAA6266CASEVCQ7933107.0351288AATCTTGTGATGAGTGGGACG6267NLVMSGT7934107.02251289CAATCACTCAAAGACGGCACT6268QSLKDGT7935106.9911290GCGTTGAATGGTTCTGGTATT6269ALNGSGI7936106.9761291AGACACGTCGTCCCCGACTCC6270RHVVPDS7937106.97051292CTGTATCATGATTCGCATCTT6271LYHDSHL7938106.9631293GGGAGTACGCCTATTACTTCT6272GSTPITS7939106.9571294CCCAACGACCAAATCAGCGGA6273PNDQISG7940106.9361295AGTGGAAAACAAGACAAATAC6274SGKQDKY7941106.9251296AGTGGGCATGCTTCTCAGGGT6275SGHASQG7942106.86751297AAGATGGGGAGTATTGAGGTT6276KMGSIEV7943106.8641298TCAACTTTAGACCGAAGCGAA6277STLDRSE7944106.86151299ACGGAGCTTAGTGAGTATACT6278TELSEYT7945106.8521300GCCAACGGAGGAGGATACCCC6279ANGGGYP7946106.8471301GTAACCGAATCTAACTCTCTA6280VTESNSL7947106.831302CCAGTCTACGACCGCGACGTC6281PVYDRDV7948106.8121303GATAATAATAAGCATGGTACT6282DNNKHGT7949106.8061304ATCTACGAAACCGTAACCTTG6283IYETVTL7950106.8011305ACTCAGACTGGTCATGTTTCT6284TQTGHVS7951106.78681306CAAGCCGACCTCAGGTACAAA6285QADLRYK7952106.7731307TGTAAGACGAATAATGCTGGT6286CKTNNAG7953106.7491308GCCGGTCACCAACAACTGGCC6287AGHQQLA7954106.74591309GATAGGGATATGGAGGGTGTT6288DRDMEGV7955106.7421310GATCAGCCGGGGTATGTGCGT6289DQPGYVR7956106.73871311GATGCTATGCTTGCTCATCCG6290DAMLAHP7957106.7351312GCCCTTAACCTGTACTCCAGC6291ALNLYSS7958106.7321313CTACTATCTAAAGGGGACTCC6292LLSKGDS7959106.7091314TCGAGTATTAGTCTGCGGTAT6293SSISLRY7960106.6451315GGGTCGAGCCAACACCACGAA6294GSSQHHE7961106.621316TCGATTGGGTATTCGCCTCCG6295SIGYSPP7962106.57731317CACTCCAACGCGACTACGATA6296HSNATTI7963106.5671318TCGGCACACGACGCAAGACTA6297SAHDARL7964106.56651319GTTCACACCGCAGACACAATA6298VHTADTI7965106.5641320CGAGACGGCTCTACTAAAGTT6299RDGSTKV7966106.558551321TTGCAGGAGTCTCTTCCTGGT6300LQESLPG7967106.5421322TTAGACTACACCCCTCAAAAC6301LDYTPQN7968106.5191323GGACCAAGTTCGCACATCGTT6302GPSSHIV7969106.5071324AGCGCCGACACCCGGTCCCCC6303SADTRSP7970106.4661325ATGATGAAGAGTGAGGAGAAT6304MMKSEEN7971106.4251326GGTATGACGAGTGAGTTGACG6305GMTSELT7972106.4171327GTAGACACCTACAGCGGTCTG6306VDTYSGL7973106.4151328GGGATGAGGGATACGCCGCCG6307GMRDTPP7974106.3851329GAGCATGATGTGAGTACGCGT6308EHDVSTR7975106.3021330GAGGTGGTGAAGACTACTCAT6309EVVKTTH7976106.2691331GTTTACGACAACGTTTCTTCT6310VYDNVSS7977106.2681332CTCATGAAAGACATGGAATCC6311LMKDMES7978106.26091333CCTCTTCATGTTGCTTCTCCT6312PLHVASP7979106.2391334GAAGTACGCGACCAAAAAACA6313EVRDQKT7980106.20751335CCAACTCCCTACTACACCGCC6314PTPYYTA7981106.1241336AACAACTACGCCTACTCCGCT6315NNYAYSA7982106.10851337CTTGTTGATACGGATAGGAAT6316LVDTDRN7983106.1081338TATCCGGCTGATCATCGGACT6317YPADHRT7984106.0881339TCTGCAACAACGAACCACGGA6318SATTNHG7985106.0661340CGTGATGATCAGCAGCTTGAT6319RDDQQLD7986106.0641341GGAGCGGGACAATCTCACGTG6320GAGQSHV7987106.03511342GATAGGACTTATCATGAGGTG6321DRTYHEV7988105.9961343GATGGTAATAATACGACTTAT6322DGNNTTY7989105.991344GTGCATATGGAGTCGTATGCG6323VHMESYA7990105.9831345TGGTACGAAACAATCAGCCCG6324WYETISP7991105.9591346CTGTTGGGGGCTCATCAGCCG6325LLGAHQP7992105.90021347CACGTACCTAACACTGAAGCA6326HVPNTEA7993105.8931348AATTCTCAGAATCCTCAGGGT6327NSQNPQG7994105.88951349CTACAAGACCGGGCAACGAAC6328LQDRATN7995105.8641350ATTGTGAATCAGCATTCGGAG6329IVNQHSE7996105.8321351TTTGAGCAGGGTAAGGTTGAG6330FEQGKVE7997105.8111352GTGGCGACGGGTGTGTTTGCT6331VATGVFA7998105.8081353GACAAAATACAAAACGAAACA6332DKIQNET7999105.7841354ACGGACAACCCGTCCTACAAA6333TDNPSYK8000105.7711355GGCGTGAACACAAAAATCGAA6334GVNTKIE8001105.76651356GGCTCTCACAACGGCCCAGCC6335GSHNGPA8002105.7631357TCCAACATGGGCGTAGCCTCT6336SNMGVAS8003105.761358AACACGGACACTAACGAAAAA6337NTDTNEK8004105.7591359TCTGCGCTTTTGCGGATGGAT6338SALLRMD8005105.7071360CCTCAACTAAGCGGCACAGCG6339PQLSGTA8006105.69141361TCTATTGTTAATAATGGGGCT6340SIVNNGA8007105.6841362AGCCTAGACCACGCCCCTCTA6341SLDHAPL8008105.6611363GACCACTCGAAACAAAACTCT6342DHSKQNS8009105.6531364CACAGTGACATGGTCAGCGGC6343HSDMVSG8010105.6421365CAGCATCGTGCGCAGGATGTG6344QHRAQDV8011105.56081366GGTAGTACTAAGTCTGGGCAG6345GSTKSGQ8012105.55091367ACAATGAGCGTAACTCTGGAA6346TMSVTLE8013105.5261368TATAATAATGGTGGGCATGTT6347YNNGGHV8014105.5161369GGTACTGCTGAGAATACGAGT6348GTAENTS8015105.4941370AATAGTTATGATGCGACGAGG6349NSYDATR8016105.4881371AGCGTCAACAACATGCGACTC6350SVNNMRL8017105.44771372CTTAACTTACAATACACTCTG6351LNLQYTL8018105.4431373GAGGCGCAGACCGGCTGGGTT6352EAQTGWV8019105.4431374CCCGCTGAAGGAAACAACCGT6353PAEGNNR8020105.4421375TCTCTGGGTGGGAATCCGCCT6354SLGGNPP8021105.43351376TATAATAGGGATAATGGTTCT6355YNRDNGS8022105.42851377TTGACTGATCCTAAGGGGCAG6356LTDPKGQ8023105.4041378ACCCCAACAGGCACCAACAAA6357TPTGTNK8024105.4031379GTTCACGCTAACGCTACATTA6358VHANATL8025105.381380CGCGAAATAGTGCACTCAAAC6359REIVHSN8026105.3761381TACGCCGTCGCGATAGGCACA6360YAVAIGT8027105.3661382AACACAACACCTCCCGACCAC6361NTTPPDH8028105.3481383GTTATTCAGTCTGATAATACG6362VIQSDNT8029105.321384GTTCCGGCGCATTCTCGGGGT6363VPAHSRG8030105.3051385CAAAACAGTGACCTCGCCAGC6364QNSDLAS8031105.2961386CGCATCGTAGACACGTTGGGA6365RIVDTLG8032105.28251387CACACTTACTCACAAGCAGAC6366HTYSQAD8033105.2671388ACGGCTCCATCCGTAGGGTCT6367TAPSVGS8034105.2591389AACGTGGGCACCGACAGAGAC6368NVGTDRD8035105.2311390GGGATTAATCGTACTAGTGAG6369GINRTSE8036105.21451391GTAGAAACAGACAGCTTAATA6370VETDSLI8037105.1951392CACTCCGCAGCGGGTGACGGT6371HSAAGDG8038105.1951393GATGCTGGGATTAGTTCTTAT6372DAGISSY8039105.1021394TGCACCGCCACAAAATGCTCA6373CTATKCS8040105.09591395CGCATAGACACTCTCCTAGTC6374RIDTLLV8041105.0891396GTATCACAATCACACGACGTG6375VSQSHDV8042105.0871397GCACTACCATCCCACTCCTCC6376ALPSHSS8043105.0591398GGGAAACCTGCGGAAGCGCCG6377GKPAEAP8044105.0551399TGGAATAGTCCGGGTGAGGCG6378WNSPGEA8045105.0531400AGGCTGGAGCGTCCGGATTAT6379RLERPDY8046105.041401ACGCGGGAGAGTCTGGTGGAT6380TRESLVD8047105.0221402AGACACGAAGGTCCGTACTCC6381RHEGPYS8048105.0021403GTTTTGTCTGATAAGGCGTTT6382VLSDKAF8049104.9811404ACTAGTGCGACTGATTCGATG6383TSATDSM8050104.9081405ACTGAGCCGCTTCCGATGTCT6384TEPLPMS8051104.8691406ATGCCTTACGTCGGGACAGTA6385MPYVGTV8052104.8381407CGTGATTATTCTCCTACTGAT6386RDYSPTD8053104.8361408CGGAATGGTGGTACTACGGAT6387RNGGTTD8054104.76251409ATGATGGGCGCGACAACGAAA6388MMGATTK8055104.75031410GCTGCCGTTGGCGGAGACACC6389AAVGGDT8056104.7421411CTTGTGAATAATGATGGGACT6390LVNNDGT8057104.72551412AGTTCGACTCCGCAGGATACT6391SSTPQDT8058104.7131413AGTCTGCGGATGGAGAATAGT6392SLRMENS8059104.70251414GTGCAGGGGCAGACCGGCTGG6393VQGQTGW8060104.6881415CTAGGTTTCACACCCCAACCG6394LGFTPQP8061104.6771416TCGGTTGCTAAGGATCAGACG6395SVAKDQT8062104.6751417CCGCGGCATGAGTTGAGTAAT6396PRHELSN8063104.6451418AAAATGGGATCGAACCCCGCA6397KMGSNPA8064104.62411419GAGGCGACTCATGGTTCTTAT6398EATHGSY8065104.6131420CCTGAGGTTGCGTGTCCTGGG6399PEVACPG8066104.5951421GTGAATACGCGGGAGGTTACG6400VNTREVT8067104.5831422ACGGCTCGTGCGATTGATATG6401TARAIDM8068104.5511423ACCGACGGCGCCCTGGGTTAC6402TDGALGY8069104.53251424GGGTCGCAATACGCGAACCGC6403GSQYANR8070104.5241425GAAATGGGTAACCAATACCCA6404EMGNQYP8071104.4531426CCGTCGACACTCGCTGAAACA6405PSTLAET8072104.4491427CGCATAGGCGTTGGAGCACCA6406RIGVGAP8073104.44051428CTGAGTGTGAAGGAGGAGATT6407LSVKEEI8074104.4351429TATACTACTCATGAGAGTGGG6408YTTHESG8075104.4331430CTTACTGCTGTTCTGACTGTT6409LTAVLTV8076104.4241431CTGCAGACTTCTGTTGCTACT6410LQTSVAT8077104.421432ACTGTGCGTTCGCCTCAGCCG6411TVRSPQP8078104.3911433CATCCTGATGGTACTCGGCCG6412HPDGTRP8079104.3751434GGAGTAACAATCGGTAGCAGG6413GVTIGSR8080104.37321435ACATACGCCTCTACTGAAGCG6414TYASTEA8081104.36751436AGGAGTAGTCCTGCGACGAAT6415RSSPATN8082104.3551437ATCGGGTCGCCGTTGGCCAAC6416IGSPLAN8083104.351438GCGTCGACTGAGTCTCATGTG6417ASTESHV8084104.3441439ATTGCGCAGAATGAGACGTAT6418IAQNETY8085104.3361440ATGGAGTCTAAGCCGTGGCAG6419MESKPWQ8086104.3071441TTAGAAAACCCAACACCAGCA6420LENPTPA8087104.3051442CCCAACCCCAGTCCAAGACAA6421PNPSPRQ8088104.2581443TCGACTAGTAATCCGCCTTAT6422STSNPPY8089104.2421444TATTTGACGGATACTCCTACT6423YLTDTPT8090104.2411445ATACGTGCATTGATGACGGAC6424IRALMTD8091104.2371446CCTATGGGTACGGATACGGTT6425PMGTDTV8092104.2211447ACGAGGACTCAGGGGACGTCT6426TRTQGTS8093104.196251448TCTAATAATATGAATCAGGCG6427SNNMNQA8094104.1871449GAAGACTCTGTAAACCACATC6428EDSVNHI8095104.1851450TCTGTTGTGCCTACGGATAAG6429SVVPTDK8096104.1741451GTGCGCGGCGTTCAAGACGCC6430VRGVQDA8097104.1671452CATGATGTGACTGTGCGGAAT6431HDVTVRN8098104.1641453CATAATAATCATGCGGGTGAG6432HNNHAGE8099104.1531454GGTAATATGAATCATAGTATT6433GNMNHSI8100104.151455GGTGTGCATACTCATACTGTT6434GVHTHTV8101104.1391456TTTTTGCCGCAGCTGGGGCAG6435FLPQLGQ8102104.0941457TTGGCCAACATGTCCGCACCA6436LANMSAP8103104.0931458GTTCGCAGAGACGAAACACCT6437VRRDETP8104104.05851459TGCCGCGACAACGTCTTAGCT6438CRDNVLA8105104.0461460ATGTTGGCTTCTCGGGTGCCT6439MLASRVP8106104.02051461GTCAGAACAGTCCTTCAACAA6440VRTVLQQ8107104.0171462TCGAATCAGAATGTGGATTGG6441SNQNVDW81081041463ACTGAGGTTACGGGGGATAGT6442TEVTGDS8109103.9651464GAAAGTGCCACATCTCTAAAA6443ESATSLK8110103.93551465AACCACCCCGCACCAAGCTCA6444NHPAPSS8111103.92351466TACGGTAACGCGAACACCGTA6445YGNANTV8112103.921151467CAAAACGACAAATCTGACAAC6446QNDKSDN8113103.91651468AGTCAGGCTCAGATTCGTGTT6447SQAQIRV8114103.9151469TTTCAGCGTGATGTTGGTCAT6448FQRDVGH8115103.86511470CTGATGAATCGTAATGCTCCT6449LMNRNAP8116103.86481471GCGGGCAGTTCGCCATCACGC6450AGSSPSR8117103.86351472TTATTCCACAGCCAAATGACC6451LFHSQMT8118103.8491473ATGATGTCTAACAGCCTCGCG6452MMSNSLA8119103.82751474GTTACCACCGTCCTCCAATCA6453VTTVLQS8120103.8181475GGTAGTCAGCGTGCTATGAAT6454GSQRAMN8121103.80861476GCATCCGGCGCACGCTACGTC6455ASGARYV8122103.79811477AAAAACTACGACAGTGACTCA6456KNYDSDS8123103.7941478GTGGGTTCTGGGGTTGGGGTT6457VGSGVGV8124103.7931479CGTTCTGACCTTACTGAAAGT6458RSDLTES8125103.7361480AGGGCGGAGTTTATTGATACG6459RAEFIDT8126103.7351481ACATCTGAAATGCGGACAGCC6460TSEMRTA8127103.7251482GAGTTGGATCATCTTTCGCAT6461ELDHLSH8128103.7141483ACACAAGCAGGTCTTGCGTCA6462TQAGLAS8129103.6961484GCGGCTCAGCATCATGATACG6463AAQHHDT8130103.6931485GGCGGCGCACACACTCGTGTA6464GGAHTRV8131103.6761486GCCTACGGTATACACGAAGTG6465AYGIHEV8132103.6531487GCGATGCTGCGTATGGAGCAG6466AMLRMEQ8133103.6521488ACGGATCGTTCGCGGCTGGGG6467TDRSRLG8134103.6221489GAGAGGGAGCCTCCTAAGAAT6468EREPPKN8135103.6211490GTTGTTAAGGAGATTAAGCTG6469VVKEIKL8136103.61251491CACACCGGCCAAACACCATCA6470HTGQTPS8137103.59451492GTGTCTCTGAGTTCGCCTCCG6471VSLSSPP8138103.5631493GGGGCAGGAAACCTGGGTACC6472GAGNLGT8139103.56151494GCACGAGACGACACGATACAA6473ARDDTIQ8140103.5231495GGGACTTATACTAATATGCCG6474GTYTNMP8141103.5221496ATGCTGGGGGGTTTTGCGCAG6475MLGGFAQ8142103.50511497CCATCCGAAATGAGGGCCGTA6476PSEMRAV8143103.5031498CGTATAAGCCCAGAAAACTCA6477RISPENS8144103.4971499AAGATGGGTGGTTCTCAGAGT6478KMGGSQS8145103.4771500GGTTTGATGGCGCATGTGACT6479GLMAHVT8146103.4641501TCACGTCAAACAGCGCTAACA6480SRQTALT8147103.45991502AGTGATCTGAATCTTCCGCCG6481SDLNLPP8148103.4551503TATGTGTCTGATTATTTGCAT6482YVSDYLH8149103.3931504ACTAATGATAATAGTGATCGT6483TNDNSDR8150103.3741505TACTTAATGCACGACAGCGCA6484YLMHDSA8151103.3691506GGCTCTCGGAACGGACCCACA6485GSRNGPT8152103.30961507AAAAACGGTGTTATAAACGAC6486KNGVIND8153103.2921508GAGTCTGTTGCTAATCTTAAG6487ESVANLK8154103.1621509GCATCGGACTCGACGACACCA6488ASDSTTP8155103.1491510CTGAACGTTAGTTCATCCAAA6489LNVSSSK8156103.1491511GAGGCTAAGGGTTTTGGTCAT6490EAKGFGH8157103.12281512GGTACGAGTGCGGAGAGTCGG6491GTSAESR8158103.1111513ATGCACAACCTACCCTCATAC6492MHNLPSY8159103.101451514GTCTTCACAGAAATAGAATCG6493VFTEIES8160103.1011515ACTCAAACTTCTACCTGGACC6494TQTSTWT8161103.0941516CCTATGAATAAGGATATTTTG6495PMNKDIL8162103.071517AAAGAATCTGAATACAGAGTT6496KESEYRV8163103.071518TCGACGAATTCTGAGGCGGTT6497STNSEAV8164103.0681519GATACGGCGAATCGTTCGACT6498DTANRST8165103.037151520CCTAAGGCTCCGCTTAATAAT6499PKAPLNN8166103.0321521TTAGCTACATACCCCTCCCAC6500LATYPSH8167103.0281522GCTACGGTTCAGTCGGTTGAT6501ATVQSVD8168103.0111523AATTCGATGGGTAATGGGGGT6502NSMGNGG8169103.0091524GATCATAGTGAGCAGAATTCG6503DHSEQNS8170102.9951525ACTTTTTTGCCTCAGCTTGGG6504TFLPQLG8171102.9941526GGGTTTACTAATACGAGTAAG6505GFTNTSK8172102.98951527ACGATGAATTATAGTCATACT6506TMNYSHT8173102.9621528AGTATCGGATTCTCAGTAGGC6507SIGFSVG8174102.95651529AGTGAGAATCGGGCTGGTAAT6508SENRAGN8175102.9451530AGTCTTAATCTGCATAGTGTG6509SLNLHSV8176102.931531CATGAGAGTCATTATGTTAGT6510HESHYVS8177102.9211532AATGTTGTTAATGGGATGGAT6511NVVNGMD8178102.9081533CACTCCGACAAAGTCTCCTCA6512HSDKVSS8179102.89921534AAATCTGTAGGCGACGGGAGA6513KSVGDGR8180102.89791535AGGCAGGTTGAGCAGTCTGAT6514RQVEQSD8181102.8891536AGGGAGCTGGTGAATACGGAT6515RELVNTD8182102.871537AACTACAGGGACATCACAATG6516NYRDITM8183102.86051538GCCAGCCTTGACCGCCTTCCA6517ASLDRLP8184102.8571539AGACAACTTGCTTCTCTCCCA6518RQLASLP8185102.8461540GTCAGCAAAACCAAAGACTCG6519VSKTKDS8186102.8321541AACGTATACGAAGGGCACCGC6520NVYEGHR8187102.8151542CTAGAACAACTACGGGTCCCA6521LEQLRVP8188102.8151543ATGACCTACACATCCCCAACC6522MTYTSPT8189102.8071544AACTCCCACACCGACAGAGGA6523NSHTDRG8190102.8011545GTGGCTGGGGGGACTTCGGAG6524VAGGTSE8191102.7891546GTCGACGCACACAGGGCTAAC6525VDAHRAN8192102.771547CGGGCAGACATGACTCCCTTA6526RADMTPL8193102.771548GGACACGAACAAACTGACGCA6527GHEQTDA8194102.7641549TACATCGCGGGAGGCGACCAA6528YIAGGDQ8195102.751550TACGGCGACCTAACTACAGTC6529YGDLTTV8196102.7371551AGATTAGACCTGCAAGAACAC6530RLDLQEH8197102.7191552CACCTTAACCCGGCGGCCCAA6531HLNPAAQ8198102.7191553GGGGTTAACGAACAAACAAAC6532GVNEQTN8199102.7031554CGTCGGTTGAGTACGGATCTT6533RRLSTDL8200102.7021555GGATCCACAGGCCTACCCCCG6534GSTGLPP8201102.70151556GACGACATGGTCAAAAACTCA6535DDMVKNS8202102.68151557GTTATAGACCTAGTCACTCGC6536VIDLVTR8203102.6731558GGAGGCCTTACCAACGGTCTA6537GGLTNGL8204102.671559CGTATGGAGGAGACTGCTTAT6538RMEETAY8205102.65351560ACCGACATCTCCGGTTACGGA6539TDISGYG8206102.6421561CAGGTTAATCATAATACTAGT6540QVNHNTS8207102.6371562GCGACTACTGAGGATGTTCGT6541ATTEDVR8208102.6261563TGGAGCATCAAAAACCAAACA6542WSIKNQT8209102.5861564TCCCCTACCAGCAACACAATA6543SPTSNTI8210102.5841565ATGAAAAACTCTGGATTCGAC6544MKNSGFD8211102.5831566CTTGTTGCTGAGCGTTTGCCG6545LVAERLP8212102.5521567GGTGAAACTAACTTCCCAACT6546GETNFPT8213102.5321568AATGGTAAGCTGGGTACGACT6547NGKLGTT8214102.527351569AACTTAGTAGCGTACACGAAA6548NLVAYTK8215102.52451570TGGCAGCTTACGACGAGTCAT6549WQLTTSH8216102.4971571AGTTTGGACCTAGGAGGCAAC6550SLDLGGN8217102.4911572AACGAAAGCACCAAAGAATCT6551NESTKES8218102.4831573GGTTTTGATGGTAAGCAGCTT6552GFDGKQL8219102.4621574CATCTGTATATTTCGGCGGAT6553HLYISAD8220102.4421575TTACTTCCAAACAACACCCAC6554LLPNNTH8221102.4241576TCCGGAATGGCCGGCCTTTCC6555SGMAGLS8222102.4231577ATCACCTCACTCCCCGAAACC6556ITSLPET8223102.4141578GAGCTTAAGGAGAGTCAGAAG6557ELKESQK8224102.4081579AATATTGTGCAGGATTATCCG6558NIVQDYP8225102.4041580TCAGAAAACACCTCTGTACCC6559SENTSVP8226102.3881581GACCCCAACCAACCCAAAACA6560DPNQPKT8227102.3761582GCGGGTTTGGATGTGAATACG6561AGLDVNT8228102.3721583TCTCATGAGATGAATAATGGT6562SHEMNNG8229102.3661584TCTTACGCCATAAACCAATCA6563SYAINQS8230102.3351585GGTCATCTGCCTGCGGCTAAG6564GHLPAAK8231102.3151586GAGTTGGGTAATAAGACGGCT6565ELGNKTA8232102.3111587CTTGAGTCTACTCGTAAGGCT6566LESTRKA8233102.311588ACTCAAGGCAACTCTGAAGCA6567TQGNSEA8234102.311589ATCTCTATAGACTCCGCTATG6568ISIDSAM8235102.3011590GAGTTTCAGAGGATTCGTGAG6569EFQRIRE8236102.2591591GCTAGTCTCTCCGCACCAGCC6570ASLSAPA8237102.2271592GACAGCCAAATCACAAGACTA6571DSQITRL8238102.2181593GGCCACGAAAACATGGGCGTG6572GHENMGV8239102.2151594ATGTCGGCGGGGCATCCTACG6573MSAGHPT8240102.2071595CACGCTCCAAGCGGCGCCATA6574HAPSGAI8241102.21596ACGACTATTACTAATTCGGTT6575TTITNSV8242102.1871597CCTCAGCATCAGCATGAGCAT6576PQHQHEH8243102.18051598CAATACTCGATGGACACGCGC6577QYSMDTR8244102.1731599CTTTATGAGGTTGGTACTCCT6578LYEVGTP8245102.1651600GGTGAGACTATGCGTCATAAT6579GETMRHN8246102.1191601ATGACAATAACCGTCGAACCG6580MTITVEP8247102.0961602GCGCAGCATCCTGAGCGTTCG6581AQHPERS8248102.0841603ACGCATGTTGCTAAGCCTGAT6582THVAKPD8249102.0821604ATGACTGCTAACTTGGTGGAA6583MTANLVE8250102.0761605AATAGGCAGCGGGATTTTGAG6584NRQRDFE8251102.0731606TCAAACAGCGCCGACGCGGGG6585SNSADAG8252102.0471607GGTGAGTATGGTGCGTCGGTT6586GEYGASV8253102.0371608GACGGCATGGTCAGGTCGACA6587DGMVRST8254102.0251609AATGGTCAGCTGCTGGCTAAT6588NGQLLAN8255102.0231610TCCGCGGGGATGACATTGGAC6589SAGMTLD8256102.0161611GATCATGTGCATCTGACTTAT6590DHVHLTY8257102.0081612ACGACACTAACGCAAACGGAC6591TTLTQTD8258102.0031613GTGCAGTTGGCTGATGGGCAT6592VQLADGH8259102.0031614ACTGACTCATCTGCAGACTCC6593TDSSADS8260101.9811615GCGATGAATGTGCGGAGTGAT6594AMNVRSD8261101.98051616GGTGATATTTCTTATAGGGTT6595GDISYRV8262101.9771617ATGGGGTATGTTGATAGTCTG6596MGYVDSL8263101.9531618CTTTATTTGGCGGCGGCTTCG6597LYLAAAS8264101.9481619TCATCCCCAGACTCGTACAGA6598SSPDSYR8265101.9211620AGTTATAATGTGGATCTGCAT6599SYNVDLH8266101.8921621CAACACACCGCCCACCCCATG6600QHTAHPM8267101.8921622GCAGTTATGGCTACACACCCC6601AVMATHP8268101.871623ATTAGTCCGAGTGCTTCTAAT6602ISPSASN8269101.8551624ACTTTGGATAATAATCATTCT6603TLDNNHS8270101.8331625AGTGGGTCTTATGTGGCGACG6604SGSYVAT8271101.8061626ATGGCGGCTCCGCCGGAGCAT6605MAAPPEH8272101.8021627CAGACTGCGTCTGGTGATACT6606QTASGDT8273101.77251628GAGTCTAAGACTGTGGTTATT6607ESKTVVI8274101.76951629ACGGTATTACCACAATCAGAC6608TVLPQSD8275101.7441630CCATTAAACGCGAACGGCTCC6609PLNANGS8276101.74151631CCCCTGAACACAGGATTAACC6610PLNTGLT8277101.7181632GCCATAACGATAATAGGCACT6611AITIIGT8278101.7111633AATCCTAGTGCGATTAGTTAT6612NPSAISY8279101.6871634ACAGAACACGAAAAATCCACT6613TEHEKST8280101.662051635GCTGAGAGTCAGCTGGCGTCG6614AESQLAS8281101.6551636GTGCTTAAGGGTACGTTTCCG6615VLKGTFP8282101.6521637TCGTTCGCCGAAATAACGACT6616SFAEITT8283101.6511638CCGTTAAACGGCCGCGTAACC6617PLNGRVT8284101.6421639TCCGAACGCCCCCAATCGTCA6618SERPQSS8285101.5791640GCTCAGCTTCAGGATTCGGTG6619AQLQDSV8286101.5681641CCCAACCGTGTAACAGCACCC6620PNRVTAP8287101.55421642GCGCTTATTGTTTCGAGTATG6621ALIVSSM8288101.541643GCGCATGGTGCTTTTCCGGTT6622AHGAFPV8289101.4951644GAGGCTTATCAGACTGAGAAG6623EAYQTEK8290101.491645GCTGCGGCTTCGCCTTTGGCT6624AAASPLA8291101.4841646CCCCAAGCCACTCTCAACAAC6625PQATLNN8292101.4321647ACGAGGGGTGATATGGAGTTT6626TRGDMEF8293101.4241648AGCAACCTAGGCGAAGCATCT6627SNLGEAS8294101.4231649GGAATCACCGGAAGCCCCGGC6628GITGSPG8295101.421650GGGTTTGAGACGAGTAGTCCT6629GFETSSP8296101.3691651CCCGCGAGAAGCGACGCCCTT6630PARSDAL8297101.3591652CATGCTAATTATGTTGAGGTG6631HANYVEV8298101.3451653GTGACTCGTAGTACGAAGGAG6632VTRSTKE8299101.323811654GATGTTGCGTTGAGGTCGAAT6633DVALRSN8300101.2541655GAGTCTGATTTGCGTCAGCGG6634ESDLRQR8301101.2251656CCGTTACTCGCAGCGAACCCG6635PLLAANP8302101.2071657ATAAACGCCGCGCACAGGCCC6636INAAHRP8303101.1631658GCTCGGAGAGACGTAAACTCG6637ARRDVNS8304101.151659AGTATGGATAAGGTGGAGAAG6638SMDKVEK8305101.1441660AACGTCAGCGCACGGGAAACA6639NVSARET8306101.1131661CTGACGACGGCTGGTATGTGG6640LTTAGMW8307100.96051662GCGCGGGCAGAAGGGGTCTTC6641ARAEGVF8308100.93251663CCGAGTGATCATATGCGGACT6642PSDHMRT8309100.88491664AGTAGGACGGTTATTTTGTCG6643SRTVILS8310100.86971665CAGAGTAATGCTGCTGAGGGT6644QSNAAEG8311100.81521666TGGACCGAAACGGCCGCTCAC6645WTETAAH8312100.77531667AAGGAGAATCAGCTTAGTAAG6646KENQLSK8313100.7556TABLE 4RGD Motifs from expression by a CK8 promoterRankSequenceSEQ ID NO: 1RGDLSTP13 2RGDLNQY14 3RGDLTTP15 4RGDATEL16 5RGDQLYH17 6RGDLSTP18 7RGDVAAK19 8RGDLTTP20 9RGDLNQY2110RGDTMSK2211RGDVAAK2312RGDTMSK2413RGDATEL25TABLE 5RGD Motifs from expression by MHCK7 promoterRankSequenceSEQ ID NO: 1RGDLTTP26 2RGDLNQY27 3RGDLSTP28 4RGDQLYH29 5RGDTMSK30 6RGDATEL31 7RGDLSTP32 8RGDMINT33 9RGDLNQY3410RGDTMSK3511RGDLTTP3612RGDLNDS37TABLE 6RGD Motifs from expression by MHCK7 and CK8combined.RankSequenceSEQ ID NO: 1RGDLSTP38 2RGDLSTP39 3RGDLTTP40 4RGDLNQY41 5RGDQLYH42 6RGDATEL43 7RGDTMSK44 8RGDLNQY45 9RGDLTTP4610RGDMINT4711RGDTMSK4812RGDTMNY4913RGDATEL50In some embodiments, the n-mer motif is or includes an “RGD” motif. An “RGD” motif refers to n-mer motifs having the presence of the amino acids R, G, D and as the three consecutive amino acids in that order of the n-mer motif. In some embodiments, the RGD motif can have the general formula XmRGDXn, where m can be 0-4 amino acids, n can be 0-15 amino acids, and where X is any amino acid, where each amino acid present can each be independently selected from the others and can be selected from the group of any amino acid. It will be appreciated that when m=0 or n=0, that this means that there are no amino acids preceding the “RGD” in the RGD motif and / or there are no amino acids following the “RGD” in the RGD motif. In some embodiments, when m=0, RGD is the first three amino acids of the RGD motif. In some embodiments, when n=0, RGD is the last three amino acids of the RGD motif. In some embodiments, where m=0 and n=0, the RGD motif contains only the amino acids RGD. Exemplary RGD motifs are shown in e.g. Tables 1-6 and 8-9.In some exemplary embodiments, the RGD motif is X1RGDX2 (SEQ ID NO: 9100), X1RGDX2X3(SEQ ID NO: 9101), X1RGDX2X3X4 (SEQ ID NO: 9102), X1RGDX2X3X4X5(SEQ ID NO: 9103), X1RGDX2X3X4X5X6 (SEQ ID NO: 9104), X1RGDX2X3X4X5X6X7 (SEQ ID NO: 9105) X1RGDX2X3X4X5X6X7X8 (SEQ ID NO: 9106), X1RGDX2X3X4X5X6X7X8X9(SEQ ID NO: 9107), X1RGDX2X3X4X5X6X7X8X9X10 (SEQ ID NO: 9108), X1RGDX2X3X4X5X6X7X8X9X10X11 (SEQ ID NO: 9109), or X1RGDX2X3X4X5X6X7X8X9X10X11X12 (SEQ ID NO: 9110).In some exemplary embodiments, the RGD motif is X1X2RGDX3 (SEQ ID NO: 9111), X1X2RGDX3X4(SEQ ID NO: 9112), X1X2RGDX3X4X5 (SEQ ID NO: 9113), X1X2RGDX3X4X5X6(SEQ ID NO: 9114), X1X2RGDX3X4X5X6X7 (SEQ ID NO: 9115), X1X2RGDX3X4X5X6X7X8(SEQ ID NO: 9116), X1X2RGDX3X4X5X6X7X8X9 (SEQ ID NO: 9117), X1X2RGDX3X4X5X6X7X8X9X10 (SEQ ID NO: 9118), X1X2RGDX3X4X5X6X7X8X9X10X11 (SEQ ID NO: 9119), or X1X2RGDX3X4X5X6X7X8X9X10X11X12 (SEQ ID NO: 9120).In some exemplary embodiments, the RGD motif is X1X2X3RGDX4 (SEQ ID NO: 9121), X1X2X3RGDX4X5(SEQ ID NO: 9122), X1X2X3RGDX4X5X6 (SEQ ID NO: 9123), X1X2X3RGDX4X5X6X7(SEQ ID NO: 9124), X1X2X3RGDX4X5X6X7X8 (SEQ ID NO: 9125), X1X2X3RGDX4X5X6X7X8X9(SEQ ID NO: 9126), X1X2X3RGDX4X5X6X7X8X9X10 (SEQ ID NO: 9127), X1X2X3RGDX4X5X6X7X8X9X10X11 (SEQ ID NO: 9128), or X1X2X3RGDX4X5X6X7X8X9X10X11X12 (SEQ ID NO: 9129).In some exemplary embodiments, the RGD motif is X1X2X3X4RGDX5 (SEQ ID NO: 9130), X1X2X3X4RGDX5X6 (SEQ ID NO: 9131), X1X2X3X4RGDX5X6X7(SEQ ID NO: 9132), X1X2X3X4RGDX5X6X7X8(SEQ ID NO: 9133), X1X2X3X4RGDX5X6X7X8X9 (SEQ ID NO: 9134), X1X2X3X4RGDX5X6X7X8X9X10 (SEQ ID NO: 9135), X1X2X3X4RGDX5X6X7X8X9X10X11 (SEQ ID NO: 9136), or X1X2X3X4RGDX5X6X7X8X9X10X11X12 (SEQ ID NO: 9137).
[0229] In some embodiments, the RGD motif has the amino acids RGD as the first three consecutive amino acids of the n-mer motif (i.e. m=0). In some exemplary embodiments, the n-mer can have a sequence of RGD or RGDXn, where n can be 1-15 amino acids and X can be any amino acid, where each amino acid present can each be independently selected from the others and can be selected from the group of any amino acid. In some embodiments, the n-mer motif can be RGD (3-mer), RGDX1 (4-mer), RGDX1X2(5-mer) (SEQ ID NO: 2), RGDX1X2X3 (6-mer) (SEQ ID NO: 3), RGDX1X2X3X4(7 mer) (SEQ ID NO: 4), RGDX1X2X3X4X5 (8 mer) (SEQ ID NO: 5), RGDX1X2X3X4X5X6(9-mer) (SEQ ID NO: 6), RGD1X2X3X4X5X6X7 (10-mer) (SEQ ID NO: 7), RGD1X2X3X4X5X6X7X8(11-mer) (SEQ ID NO: 8), RGDX1X2X3X4X5X6X7X8X9 (12-mer) (SEQ ID NO: 9), RGDX1X2X3X4X5X6X7X8X9X10 (13-mer) (SEQ ID NO: 10), RGDX1X2X3X4X5X6X7X8X9X10X11(14-mer) (SEQ ID NO: 11), or RGDX1X2X3X4X5X6X7X8X9X10X11X12 (15-mer) (SEQ ID NO: 12), where X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 are each be independently selected from any amino acid. In some embodiments, X1 is L, T, A, M, V, Q, or M. In some embodiments, X2 is T, M, S, N, L, A, or I. In some embodiments, X3 is T, E, N, O, S, Q, Y, A, or D. In some embodiments, X4 is P, Y, K, L, H, T, or S. In some embodiments, n-mer motifs including the RGD motif is included in a muscle-specific engineered AAV capsids.
[0230] In some embodiments, the n-mer motif can be in any one of Tables 1-6. In some embodiments, the n-mer motif in any of Tables 1-6 and 8-9 can be included in a muscle specific engineered capsid.
[0231] In some embodiments, the n-mer motif can be in any one of Tables 4-6. In some embodiments, the n-mer motif in any of Tables 4-6 and 8-9 can be included in a muscle specific engineered capsid.
[0232] The muscle-specific targeting moiety can be coupled to or otherwise associated with a cargo. In some embodiments, one or more muscle-specific targeting moieties described herein is directly attached to the cargo. In some embodiments, one or more muscle-specific targeting moieties described herein is indirectly coupled to the cargo, such as via a linker molecule. In some embodiments, one or more one or more muscle-specific targeting moieties described herein is coupled to associated with a polypeptide or other particle that is coupled to, attached to, encapsulates, and / or contains a cargo.
[0233] Exemplary particles include, without limitation, viral particles (e.g. viral capsids, which is inclusive of bacteriophage capsids), polysomes, liposomes, nanoparticles, microparticles, exosomes, micelles, and the like. The term “nanoparticle” as used herein includes a nanoscale deposit of a homogenous or heterogeneous material. Nanoparticles may be regular or irregular in shape and may be formed from a plurality of co-deposited particles that form a composite nanoscale particle. Nanoparticles may be generally spherical in shape or have a composite shape formed from a plurality of co-deposited generally spherical particles. Exemplary shapes for the nanoparticles include, but are not limited to, spherical, rod, elliptical, cylindrical, disc, and the like. In some embodiments, the nanoparticles have a substantially spherical shape.
[0234] As used herein, the term “specific” when used in relation to described an interaction between two moieties, refers to non-covalent physical association of a first and a second moiety wherein the association between the first and second moieties is at least 2 times as strong, at least 5 times as strong as, at least 10 times as strong as, at least 50 times as strong as, at least 100 times as strong as, or stronger than the association of either moiety with most or all other moieties present in the environment in which binding occurs. Binding of two or more entities may be considered specific if the equilibrium dissociation constant, Kd, is 10−3 M or less, 10−4 M or less, 10−5 M or less, 10−6 M or less, 10−7 M or less, 10−8M or less, 10−9 M or less, 10−10 M or less, 10−11 M or less, or 10−12 M or less under the conditions employed, e.g., under physiological conditions such as those inside a cell or consistent with cell survival. In some embodiments, specific binding can be accomplished by a plurality of weaker interactions (e.g., a plurality of individual interactions, wherein each individual interaction is characterized by a Kd of greater than 10−3 M). In some embodiments, specific binding, which can be referred to as “molecular recognition,” is a saturable binding interaction between two entities that is dependent on complementary orientation of functional groups on each entity. Examples of specific interactions include primer-polynucleotide interaction, aptamer-aptamer target interactions, antibody-antigen interactions, avidin-biotin interactions, ligand-receptor interactions, metal-chelate interactions, hybridization between complementary nucleic acids, etc.
[0235] In some embodiments, in addition to the one or more n-mer motifs the targeting moiety can include a polypeptide, a polynucleotide, a lipid, a polymer, a sugar, or a combination thereof.Engineered Muscle Targeting Viral Capsids
[0236] In some embodiments, the muscle engineered muscle-specific targeting moiety is incorporated into a viral capsid protein, which can in turn be incorporated into an engineered viral capsid of an engineered virus particle, thus providing a muscle-specific virus particle. The muscle-specific engineered virus particle can be useful for delivering a cargo to muscle cells. In some embodiments, the targeting moiety is incorporated into a viral protein, such as a capsid protein, including but not limited to lentiviral, adenoviral, AAV, bacteriophage, retroviral proteins. In some embodiments, one or more n-mer motifs (such as an RGD or non-RGD n-mer motif) is located between two amino acids of the viral protein such that one or more of the one or more n-mer motifs are external (i.e. is presented on the surface of) to a viral capsid.
[0237] In some embodiments, the composition containing one or more of the muscle-specific targeting moieties described herein has increased muscle cell potency, muscle cell specificity, reduced immunogenicity, or any combination thereof.
[0238] Cargos include any molecule that is capable of being coupled to or associated with the muscle-specific targeting moieties described herein. Cargos include, without limitation, nucleotides, oligonucleotides, polynucleotides, amino acids, peptides, polypeptides, riboproteins, lipids, sugars, pharmaceutically active agents (e.g. drugs, imaging and other diagnostic agents, and the like), chemical compounds, and combinations thereof. In some embodiments, the cargo is or includes, DNA, RNA, amino acids, peptide(s), polypeptide(s), antibody(ies), aptamer(s), ribozyme(s), guide sequence(s) for ribozymes that inhibit translation or transcription of essential tumor proteins and genes, hormone(s), immunomodulator(s), antipyretic(s), anxiolytic(s), antipsychotic(s), analgesic(s), antispasmodic(s), anti-inflammatory(ries), anti-histamine(s), anti-infective(s), radiation sensitizer(s), chemotherapeutic(s), radioactive compound(s), imaging agent(s), genetic modifying agent(s), and combinations thereof.
[0239] In some embodiments, the cargo is capable of treating or preventing a muscle disease or disorder. In some embodiments, the muscle disease or disorder is (a) an auto immune disease; (b) a cancer; (c) a muscular dystrophy; (d) a neuro-muscular disease; (e) a sugar or glycogen storage disease; (f) an expanded repeat disease; (g) a dominant negative disease; (h) a cardiomyopathy; (i) a viral disease; (j) a progeroid disease; or (k) any combination thereof. In some embodiments, the expanded repeat disease is Huntington's disease, a Myotonic Dystrophy, or Facioscapulohumeral muscular dystrophy (FSHD). In some embodiments, the muscular dystrophy is Duchene muscular dystrophy, Becker Muscular dystrophy, a Limb-Girdle muscular dystrophy, an Emery Dreifuss muscular dystrophy, a myotonic dystrophy, or FSHD. In some embodiments, the myotonic dystrophy is Type 1 or Type 2. In some embodiments, the sugar or glycogen storage disease is a MPS type III disease or Pompe disease. In some embodiments, the MPS type III disease, is MPS Type IIIA, IIIB, IIIC, or IIID. In some embodiments, the neuro-muscular disease is Charcot-Marie-Tooth disease or Friedreich's Ataxia.
[0240] In some embodiments, the cargo is a morpholino, a peptide-linked morpholino, an antisense oligonucleotide, a PMO, a therapeutic transgene, a polynucleotide encoding a therapeutic polypeptide or peptide, a PPMO, one or more peptides, one or more polynucleotides encoding a CRISPR-Cas protein, a guide RNA, or both, a ribonucleoprotein, wherein the ribonucleoprotein comprises a CRISPR-Cas system molecule, a therapeutic transgene RNA, or other gene modifying or therapeutic RNA and / or protein, or any combination thereof.
[0241] In some embodiments, the cargo is capable of inducing exon skipping in a gene.
[0242] In some embodiments, the cargo is capable of inducing exon skipping in a dystrophin gene.
[0243] In some embodiments, the cargo is a mini- or micro-dystrophin gene. In some embodiments, the mini- or micro-dystrophin gene comprises spectrin-like repeats 1, 2, 3, 16, 17, and 24, and optionally an nNOS domain.Engineered Muscle Targeting AAV Capsids and AAVs
[0244] In some embodiments, the engineered muscle-specific targeting moiety is incorporated an adeno-associated virus (AAV) capsid. Described herein are various embodiments of engineered AAV capsids that can be engineered to confer cell-specific tropism to an engineered AAV particle. The engineered capsids can be included in an engineered virus particle and can confer cell-specific tropism, reduced immunogenicity, or both to the engineered AAV particle. The engineered AAV capsids described herein can include one or more engineered AAV capsid proteins described herein. In some embodiments, the AAV capsid protein comprises one or more n-mer motifs. In some embodiments, one or more of the n-mer motifs contains or is an RGD motif or a non-RGD n-mer motif. Such motifs are defined and described in greater detail elsewhere herein. In some embodiments, one or more of the one or more n-mer motifs incorporated into one or more AAV capsid proteins can confer muscle specificity to an AAV virus particle having the engineered capsid with the n-mer motif(s).
[0245] The engineered AAV capsid and / or capsid proteins can be encoded by one or more engineered AAV capsid polynucleotides. In some embodiments, an engineered AAV capsid polynucleotide can include a 3′ polyadenylation signal. The polyadenylation signal can be an SV40 polyadenylation signal.
[0246] The engineered AAV capsids can be variants of wild-type AAV capsids. In some embodiments, the wild-type AAV capsids can be composed of VP1, VP2, VP3 capsid proteins or a combination thereof. In other words, the engineered AAV capsids can include one or more variants of a wild-type VP1, wild-type VP2, and / or wild-type VP3 capsid proteins. In some embodiments, the serotype of the reference wild-type AAV capsid can be AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV rh.74, or AAV rh.10, or any combination thereof. In some embodiments, the serotype of the wild-type AAV capsid can be AAV-9. The engineered AAV capsids can have a different tropism than that of the reference wild-type AAV capsid.
[0247] The engineered AAV capsid can contain 1-60 engineered capsid proteins. In some embodiments, the engineered AAV capsids can contain 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, to / or 60 engineered capsid proteins. In some embodiments, the engineered AAV capsid can contain 0-59 wild-type AAV capsid proteins. In some embodiments, the engineered AAV capsid can contain 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, to / or 59 wild-type AAV capsid proteins.
[0248] In some embodiments, the engineered AAV capsid protein has an n-mer amino acid motif, where n can be at least 3 amino acids. In some embodiments, n can be 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acids. In some embodiments, the engineered AAV capsid can have a 6-mer or 7-mer amino acid motif. In some embodiments, the n-mer amino acid motif is inserted between two amino acids in the wild-type viral protein (VP) (or capsid protein). In some embodiments, the n-mer motif can be inserted between two amino acids in a variable amino acid region in an AAV capsid protein. The core of each wild-type AAV viral protein contains an eight-stranded beta-barrel motif (betaB to betaI) and an alpha-helix (alphaA) that are conserved in autonomous parvovirus capsids (see e.g. DiMattia et al. 2012. J. Virol. 86(12):6947-6958). Structural variable regions (VRs) occur in the surface loops that connect the beta-strands, which cluster to produce local variations in the capsid surface. AAVs have 12 variable regions (also referred to as hypervariable regions) (see e.g. Weitzman and Linden. 2011. “Adeno-Associated Virus Biology.” In Snyder, R. O., Moullier, P. (eds.) Totowa, NJ: Humana Press). In some embodiments, one or more n-mer motifs are inserted between two amino acids in one or more of the 12 variable regions in the wild-type AAV capsid proteins. In some embodiments, the one or more n-mer motifs are each inserted between two amino acids in VR-I, VR-II, VR-III, VR-IV, VR-V, VR-VI, VR-VII, VR-III, VR-IX, VR-X, VR-XI, VR-XII, or a combination thereof. In some embodiments, the n-mer is be inserted between two amino acids in the VR-III of a capsid protein. In some embodiments, the engineered capsid can have an n-mer inserted between any two contiguous amino acids between amino acids 262 and 269, between any two contiguous amino acids between amino acids 327 and 332, between any two contiguous amino acids between amino acids 382 and 386, between any two contiguous amino acids between amino acids 452 and 460, between any two contiguous amino acids between amino acids 488 and 505, between any two contiguous amino acids between amino acids 545 and 558, between any two contiguous amino acids between amino acids 581 and 593, between any two contiguous amino acids between amino acids 704 and 714 of an AAV9 viral protein. In some embodiments, the engineered capsid can have an n-mer inserted between amino acids 588 and 589 of an AAV9 viral protein. In some embodiments, the engineered capsid can have a 7-mer motif inserted between amino acids 588 and 589 of an AAV9 viral protein. SEQ ID NO: 1 is a reference AAV9 capsid sequence for at least referencing the insertion sites discussed above. It will be appreciated that n-mers can be inserted in analogous positions in AAV viral proteins of other serotypes. In some embodiments as previously discussed, the n-mer(s) can be inserted between any two contiguous amino acids within the AAV viral protein and in some embodiments the insertion is made in a variable region.AAV9 capsid reference sequenceSEQ ID NO: 1MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLDKGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQAKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTESVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVITTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQRLINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAHEGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENVPFHSSYAHSQSLDRLMNPLIDQYLYYLSKTINGSGQNQQTLKFSVAGPSNMAVQGRNYIPGPSYRQQRVSTTVTQNNNSEFAWPGASSWALNGRNSLMNPGPAMASHKEGEDRFFPLSGSLIFGKQGTGRDNVDADKVMITNEEEIKTTNPVATESYGQVATNHQSAQAQAQTGWVQNQGILPGMVWQDRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPPTAFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTEGVYSEPRPIGTRYLTRNL
[0249] In some embodiments, the n-mer motif can be any amino acid motif as shown or encoded by a nucleic acid as shown in Tables 1-3. In some embodiments, insertion of the n-mer motif in an AAV capsid can result in cell, tissue, organ, specific engineered AAV capsids. In some embodiments, the engineered capsid has a specificity (or tropism) for muscle cells. In some embodiments, the engineered capsid can have a specificity for bone tissue and / or cells, lung tissue and / or cells, liver tissues and / or cells, bladder tissue and / or cells, kidney tissue and / or cells, cardiac tissue and / or cells, skeletal muscle tissue and / or cells, smooth muscle and / or cells, neuronal tissue and / or cells, intestinal tissue and / or cells, pancreases tissue and / or cells, adrenal gland tissue and / or cells, brain tissue and / or cells, tendon tissues or cells, skin tissues and / or cells, spleen tissue and / or cells, eye tissue and / or cells, blood cells, synovial fluid cells, immune cells (including specificity for particular types of immune cells), and combinations thereof.
[0250] In some embodiments, the AAV capsids are muscle-specific. In some embodiments, muscle-specificity of the engineered AAV capsid is conferred by a muscle specific n-mer motif incorporated in the engineered AAV capsid. While not intending to be bound by theory, it is believed that the n-mer motif confers a 3D structure to or within a domain or region of the engineered AAV capsid such that the interaction of an engineered AAV containing said engineered AAV capsid has increased or improved interactions (e.g. increased affinity) with a cell surface receptor and / or other molecule on the surface of a muscle cell. In some embodiments, the cell surface receptor is AAV receptor (AAVR). In some embodiments, the cell surface receptor is a muscle cell specific AAV receptor. In some embodiments, a muscle specific engineered AAV containing the muscle-specific capsid can have an increased transduction rate, efficiency, amount, or a combination thereof in a muscle cell as compared to other cells types and / or other AAVs that do not contain a muscle-specific engineered AAV capsid as described herein.Methods of Generating Muscle Specific Targeting Moieties
[0251] Also provided herein are methods of generating engineered AAV capsids. The engineered AAV capsid variants can be variants of wild-type AAV capsids. FIGS. 6-8 can illustrate various embodiments of methods capable of generating engineered AAV capsids described herein. Generally, an AAV capsid library can be generated by expressing engineered capsid vectors each containing an engineered AAV capsid polynucleotide previously described in an appropriate AAV producer cell line. See e.g. FIG. 8. It will be appreciated that although FIG. 8 shows a helper-dependent method of AAV particle production, it will be appreciated that this can be done via a helper-free method as well. This can generate an AAV capsid library that can contain one more desired cell-specific engineered AAV capsid variant. As shown in FIG. 6 the AAV capsid library can be administered to various non-human animals for a first round of mRNA-based selection. As shown in FIG. 1, the transduction process by AAVs and related vectors can result in the production of an mRNA molecule that is reflective of the genome of the virus that transduced the cell. As is at least demonstrated in the Examples herein, mRNA based-selection can be more specific and effective to determine a virus particle capable of functionally transducing a cell because it is based on the functional product produced as opposed to just detecting the presence of a virus particle in the cell by measuring the presence of viral DNA.
[0252] After first-round administration, one or more engineered AAV virus particles having a desired capsid variant can then be used to form a filtered AAV capsid library. Desirable AAV virus particles can be identified by measuring the mRNA expression of the capsid variants and determining which variants are highly expressed in the desired cell type(s) as compared to non-desired cells type(s). Those that are highly expressed in the desired cell, tissue, and / or organ type are the desired AAV capsid variant particles. In some embodiments, the AAV capsid variant encoding polynucleotide is under control of a tissue-specific promoter that has selective activity in the desired cell, tissue, or organ.
[0253] The engineered AAV capsid variant particles identified from the first round can then be administered to various non-human animals. In some embodiments, the animals used in the second round of selection and identification are not the same as those animals used for first round selection and identification. Similar to round 1, after administration the top expressing variants in the desired cell, tissue, and / or organ type(s) can be identified by measuring viral mRNA expression in the cells. The top variants identified after round two can then be optionally barcoded and optionally pooled. In some embodiments, top variants from the second round can then be administered to a non-human primate to identify the top cell-specific variant(s), particularly if the end use for the top variant is in humans. Administration at each round can be systemic.
[0254] In some embodiments, the method of generating an AAV capsid variant can include the steps of: (a) expressing a vector system described herein that contains an engineered AAV capsid polynucleotide in a cell to produce engineered AAV virus particle capsid variants; (b) harvesting the engineered AAV virus particle capsid variants produced in step (a); (c) administering engineered AAV virus particle capsid variants to one or more first subjects, wherein the engineered AAV virus particle capsid variants are produced by expressing an engineered AAV capsid variant vector or system thereof in a cell and harvesting the engineered AAV virus particle capsid variants produced by the cell; and (d) identifying one or more engineered AAV capsid variants produced at a significantly high level by one or more specific cells or specific cell types in the one or more first subjects. In this context, “significantly high” can refer to a titer that can range from between about 2×1011 to about 6×1012 vector genomes per 15 cm dish.
[0255] The method can further include the steps of: (e) administering some or all engineered AAV virus particle capsid variants identified in step (d) to one or more second subjects; and (f) identifying one or more engineered AAV virus particle capsid variants produced at a significantly high level in one or more specific cells or specific cell types in the one or more second subjects. The cell in step (a) can be a prokaryotic cell or a eukaryotic cell. In some embodiments, the administration in step (c), step (e), or both is systemic. In some embodiments, one or more first subjects, one or more second subjects, or both, are non-human mammals. In some embodiments, one or more first subjects, one or more second subjects, or both, are each independently selected from the group consisting of: a wild-type non-human mammal, a humanized non-human mammal, a disease-specific non-human mammal model, and a non-human primate.
[0256] Other methods and details of developing muscle-specific targeting moieties are described in, for example, US Provisional Application Serial Nos. 62 / 899,453, 62 / 916,207, 63 / 018,454, 63 / 055,252, and 62 / 916,221 and International Application No. PCT / US20 / 50534.Engineered Muscle-Specific Targeting Moiety Encoding Polynucleotides, Vectors, and Vector Systems
[0257] Described herein are polynucleotides that encode the one or more muscle-specific engineered targeting moieties and vectors and / or vector systems thereof. In some embodiments, the encoding polynucleotides, vectors, and / or vector systems can be used to express and / or produce the engineered muscle-specific targeting moieties, couple the engineered muscle-specific targeting moiety to one or more other polypeptides, and / or produce particles, such as viral particles that optionally contain a cargo, that include one or more engineered muscle-specific targeting moieties described herein. The term “engineered muscle-specific targeting moiety polynucleotide” as used herein refers to a polynucleotide that encodes an engineered muscle-specific targeting moiety. As used herein, the term “encode” refers to principle that DNA can be transcribed into RNA, which can then be translated into amino acid sequences that can form proteins. Thus, polynucleotides said to encode a subsequent polynucleotide (such as an RNA species) or proteins can also be referred to as encoding polynucleotides and refer to DNA molecules that are subsequently transcribed and / or translated as well as RNA molecules that are translated.
[0258] Also provided herein are vectors and vector systems that can contain one or more of the engineered muscle-specific targeting moiety polynucleotides (including, but not limited to, engineered AAV capsid polynucleotides) described herein. As used in this context, engineered AAV capsid polynucleotides refers to any one or more of the polynucleotides described herein capable of encoding an engineered AAV capsid as described elsewhere herein and / or polynucleotide(s) capable of encoding one or more engineered AAV capsid proteins described elsewhere herein. Further, where the vector includes an engineered muscle-specific targeting moiety polynucleotide (including, but not limited to, an engineered AAV capsid polynucleotide) described herein, the vector can also be referred to and considered an engineered vector or system thereof although not specifically noted as such. In embodiments, the vector can contain one or more polynucleotides encoding one or more elements of an engineered viral capsid, such as an AAV capsid, described herein. The vectors and systems thereof can be useful in producing bacterial, fungal, yeast, plant cells, animal cells, and transgenic animals that can express a muscle-specific targeting moiety or composition containing a muscle-specific targeting moiety described herein. In some embodiments, the vectors and systems thereof can be useful in producing bacterial cells, fungal cells, yeast cells, plant cells, animal cells, or transgenic organisms (e.g. plants, animals) that can express the one or more components of the engineered AAV capsid described herein. Within the scope of this disclosure are vectors containing one or more of the polynucleotide sequences described herein. One or more of the polynucleotides that are part of the engineered AAV capsid and system thereof described herein can be included in a vector or vector system.
[0259] The vectors and / or vector systems can be used, for example, to express one or more of the engineered muscle-specific targeting moiety polynucleotides (including, but not limited to, engineered AAV capsid polynucleotides) in a cell, such as a producer cell, to produce engineered viral particles containing an engineered viral capsid (e.g. an AAV containing an engineered AAV capsid) described elsewhere herein. Other uses for the vectors and vector systems described herein are also within the scope of this disclosure. In general, and throughout this specification, the term is a tool that allows or facilitates the transfer of an entity from one environment to another. In some contexts which will be appreciated by those of ordinary skill in the art, “vector” can be a term of art to refer to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. A vector can be a replicon, such as a plasmid, phage, or cosmid, into which another DNA segment may be inserted so as to bring about the replication of the inserted segment. Generally, a vector is capable of replication when associated with the proper control elements.
[0260] Vectors include, but are not limited to, nucleic acid molecules that are single-stranded, double-stranded, or partially double-stranded; nucleic acid molecules that comprise one or more free ends, no free ends (e.g. circular); nucleic acid molecules that comprise DNA, RNA, or both; and other varieties of polynucleotides known in the art. One type of vector is a “plasmid,” which refers to a circular double stranded DNA loop into which additional DNA segments can be inserted, such as by standard molecular cloning techniques. Another type of vector is a viral vector, wherein virally-derived DNA or RNA sequences are present in the vector for packaging into a virus (e.g. retroviruses, replication defective retroviruses, adenoviruses, replication defective adenoviruses, and adeno-associated viruses (AAVs)). Viral vectors also include polynucleotides carried by a virus for transfection into a host cell. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g. bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively-linked. Such vectors are referred to herein as “expression vectors.” Common expression vectors of utility in recombinant DNA techniques are often in the form of plasmids.
[0261] Recombinant expression vectors can be composed of a nucleic acid (e.g. a polynucleotide) of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory elements, which can be selected on the basis of the host cells to be used for expression, that is operatively-linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, “operably linked” and “operatively-linked” are used interchangeably herein and further defined elsewhere herein. In the context of a vector, the term “operably linked” is intended to mean that the nucleotide sequence of interest is linked to the regulatory element(s) in a manner that allows for expression of the nucleotide sequence (e.g., in an in vitro transcription / translation system or in a host cell when the vector is introduced into the host cell). Advantageous vectors include adeno-associated viruses, and types of such vectors can also be selected for targeting particular types of cells, such as those engineered AAV vectors containing an engineered AAV capsid polynucleotide with a desired cell-specific tropism, such as a muscle-specific tropism. These and other embodiments of the vectors and vector systems are described elsewhere herein.
[0262] In some embodiments, the vector can be a bicistronic vector. In some embodiments, a bicistronic vector can be used for expressing one or more engineered muscle-specific targeting moiety polynucleotides (including, but not limited to, engineered AAV capsid polynucleotides) system described herein. In some embodiments, expression of an engineered muscle-specific targeting moiety polynucleotides (including, but not limited to, engineered AAV capsid polynucleotides) described herein can be driven by the suitable constitutive or tissue specific promoter. Such embodiments can be advantageous for generating muscle-specific targeting moieties, which are described in greater detail elsewhere herein. Where the element of the engineered AAV capsid system is an RNA, its expression can be driven by a Pol III promoter, such as a U6 promoter. In some embodiments, the two are combined.Cell-Based Vector Amplification and Expression
[0263] Vectors can be designed for expression of one or more engineered muscle-specific targeting moiety polynucleotides (including, but not limited to, engineered AAV capsid polynucleotides) or a system including one or more engineered muscle-specific targeting moiety polynucleotides (including, but not limited to, engineered AAV capsid polynucleotides) or product thereof described herein (e.g. nucleic acid transcripts, proteins, enzymes, and combinations thereof) in a suitable host cell. In some embodiments, the suitable host cell is a prokaryotic cell. Suitable host cells include, but are not limited to, bacterial cells, yeast cells, insect cells, and mammalian cells. The vectors can be viral-based or non-viral based. In some embodiments, the suitable host cell is a eukaryotic cell. In some embodiments, the suitable host cell is a suitable bacterial cell. Suitable bacterial cells include, but are not limited to, bacterial cells from the bacteria of the species Escherichia coli. Many suitable strains of E. coli are known in the art for expression of vectors. These include, but are not limited to Pir1, Stbl2, Stbl3, Stbl4, TOP10, XL1 Blue, and XL10 Gold. In some embodiments, the host cell is a suitable insect cell. Suitable insect cells include those from Spodoptera frugiperda. Suitable strains of S. frugiperda cells include, but are not limited to, Sf9 and Sf21. In some embodiments, the host cell is a suitable yeast cell. In some embodiments, the yeast cell can be from Saccharomyces cerevisiae. In some embodiments, the host cell is a suitable mammalian cell. Many types of mammalian cells have been developed to express vectors. Suitable mammalian cells include, but are not limited to, HEK293, Chinese Hamster Ovary Cells (CHOs), mouse myeloma cells, HeLa, U2OS, A549, HT1080, CAD, P19, NIH 3T3, L929, N2a, MCF-7, Y79, SO-Rb50, HepG G2, DIKX-X11, J558L, Baby hamster kidney cells (BHK), and chicken embryo fibroblasts (CEFs). Suitable host cells are discussed further in Goeddel, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif (1990).
[0264] In some embodiments, the vector can be a yeast expression vector. Examples of vectors for expression in yeast Saccharomyces cerevisiae include pYepSec1 (Baldari, et al., 1987. EMBO J. 6: 229-234), pMFa (Kuijan and Herskowitz, 1982. Cell 30: 933-943), pJRY88 (Schultz et al., 1987. Gene 54: 113-123), pYES2 (Invitrogen Corporation, San Diego, Calif.), and picZ (InVitrogen Corp, San Diego, Calif). As used herein, a “yeast expression vector” refers to a nucleic acid that contains one or more sequences encoding an RNA and / or polypeptide and may further contain any desired elements that control the expression of the nucleic acid(s), as well as any elements that enable the replication and maintenance of the expression vector inside the yeast cell. Many suitable yeast expression vectors and features thereof are known in the art; for example, various vectors and techniques are illustrated in Yeast Protocols, 2nd edition, Xiao, W., ed. (Humana Press, New York, 2007) and Buckholz, R. G. and Gleeson, M. A. (1991) Biotechnology (NY) 9(11): 1067-72. Yeast vectors can contain, without limitation, a centromeric (CEN) sequence, an autonomous replication sequence (ARS), a promoter, such as an RNA Polymerase III promoter, operably linked to a sequence or gene of interest, a terminator such as an RNA polymerase III terminator, an origin of replication, and a marker gene (e.g., auxotrophic, antibiotic, or other selectable markers). Examples of expression vectors for use in yeast may include plasmids, yeast artificial chromosomes, 2 plasmids, yeast integrative plasmids, yeast replicative plasmids, shuttle vectors, and episomal plasmids.
[0265] In some embodiments, the vector is a baculovirus vector or expression vector and can be suitable for expression of polynucleotides and / or proteins in insect cells. Baculovirus vectors available for expression of proteins in cultured insect cells (e.g., SF9 cells) include the pAc series (Smith, et al., 1983. Mol. Cell. Biol. 3: 2156-2165) and the pVL series (Lucklow and Summers, 1989. Virology 170: 31-39). rAAV (recombinant Adeno-associated viral) vectors are preferably produced in insect cells, e.g., Spodoptera frugiperda Sf9 insect cells, grown in serum-free suspension culture. Serum-free insect cells can be purchased from commercial vendors, e.g., Sigma Aldrich (EX-CELL 405).
[0266] In some embodiments, the vector is a mammalian expression vector. In some embodiments, the mammalian expression vector is capable of expressing one or more polynucleotides and / or polypeptides in a mammalian cell. Examples of mammalian expression vectors include, but are not limited to, pCDM8 (Seed, 1987. Nature 329: 840) and pMT2PC (Kaufman, et al., 1987. EMBO J. 6: 187-195). The mammalian expression vector can include one or more suitable regulatory elements capable of controlling expression of the one or more polynucleotides and / or proteins in the mammalian cell. For example, commonly used promoters are derived from polyoma, adenovirus 2, cytomegalovirus, simian virus 40, and others disclosed herein and known in the art. More detail on suitable regulatory elements are described elsewhere herein.
[0267] For other suitable expression vectors and vector systems for both prokaryotic and eukaryotic cells see, e.g., Chapters 16 and 17 of Sambrook, et al., MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989.
[0268] In some embodiments, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid). Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert, et al., 1987. Genes Dev. 1: 268-277), lymphoid-specific promoters (Calame and Eaton, 1988. Adv. Immunol. 43: 235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989. EMBO J. 8: 729-733) and immunoglobulins (Baneiji, et al., 1983. Cell 33: 729-740; Queen and Baltimore, 1983. Cell 33: 741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byrne and Ruddle, 1989. Proc. Natl. Acad. Sci. USA 86: 5473-5477), pancreas-specific promoters (Edlund, et al., 1985. Science 230: 912-916), and mammary gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are also encompassed, e.g., the murine hox promoters (Kessel and Gruss, 1990. Science 249: 374-379) and the α-fetoprotein promoter (Campes and Tilghman, 1989. Genes Dev. 3: 537-546). With regards to these prokaryotic and eukaryotic vectors, mention is made of U.S. Pat. No. 6,750,059, the contents of which are incorporated by reference herein in their entirety. Other embodiments can utilize viral vectors, with regards to which mention is made of U.S. patent application Ser. No. 13 / 092,085, the contents of which are incorporated by reference herein in their entirety. Tissue-specific regulatory elements are known in the art and in this regard, mention is made of U.S. Pat. No. 7,776,321, the contents of which are incorporated by reference herein in their entirety. In some embodiments, a regulatory element can be operably linked to or coupled to one or more engineered muscle-specific targeting moiety polynucleotides (including, but not limited to, engineered AAV capsid polynucleotides) and / or one or more elements of a system comprising one or more engineered muscle-specific targeting moiety polynucleotides (including, but not limited to, engineered AAV capsid polynucleotides) or product thereof so as to drive expression of the one or more elements of the engineered muscle-specific targeting moiety polynucleotides (including, but not limited to, engineered AAV capsid polynucleotides) or system thereof described herein.
[0269] Vectors may be introduced and propagated in a prokaryote or prokaryotic cell. In some embodiments, a prokaryote is used to amplify copies of a vector to be introduced into a eukaryotic cell or as an intermediate vector in the production of a vector to be introduced into a eukaryotic cell (e.g. amplifying a plasmid as part of a viral vector packaging system). In some embodiments, a prokaryote is used to amplify copies of a vector and express one or more nucleic acids, such as to provide a source of one or more proteins for delivery to a host cell or host organism.
[0270] In some embodiments, the vector can be a fusion vector or fusion expression vector. In some embodiments, fusion vectors add a number of amino acids to a protein encoded therein, such as to the amino terminus, carboxy terminus, or both of a recombinant protein. Such fusion vectors can serve one or more purposes, such as: (i) to increase expression of recombinant protein; (ii) to increase the solubility of the recombinant protein; and (iii) to aid in the purification of the recombinant protein by acting as a ligand in affinity purification. In some embodiments, expression of polynucleotides (such as non-coding polynucleotides) and proteins in prokaryotes can be carried out in Escherichia coli with vectors containing constitutive or inducible promoters directing the expression of either fusion or non-fusion polynucleotides and / or proteins. In some embodiments, the fusion expression vector can include a proteolytic cleavage site, which can be introduced at the junction of the fusion vector backbone or other fusion moiety and the recombinant polynucleotide or protein to enable separation of the recombinant polynucleotide or protein from the fusion vector backbone or other fusion moiety subsequent to purification of the fusion polynucleotide or protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase. Example fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith and Johnson, 1988. Gene 67: 31-40), pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) that fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein. Examples of suitable inducible non-fusion E. coli expression vectors include pTrc (Amrann et al., (1988) Gene 69:301-315) and pET 11d (Studier et al., GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 60-89).
[0271] In some embodiments, one or more vectors driving expression of one or more engineered muscle-specific targeting moiety polynucleotides (including, but not limited to, engineered AAV capsid polynucleotides), vector, and / or vector system thereof described herein are introduced into a host cell such that expression of one or more the engineered muscle-specific targeting moiety polynucleotides (including, but not limited to, engineered AAV capsid polynucleotides), vectors, and / or vector systems described herein direct formation of an engineered muscle-specific targeting moiety and / or compositions or engineered muscle-specific delivery systems that include one or more engineered muscle-specific targeting moieties described herein. In some embodiments, the engineered muscle-specific delivery system is a viral particle such as an engineered AAV particle that contains an engineered capsid that contains one or more engineered muscle-specific targeting moieties described elsewhere herein. For example, different elements of an engineered muscle-specific delivery system can each be operably linked to separate regulatory elements on the same or separate vectors. RNA(s) of different elements of the engineered muscle-specific delivery system described herein that can include one or more engineered muscle-specific targeting moiety can be delivered to an animal or mammal or cell thereof to produce an animal or mammal or cell thereof that constitutively, inducibly, or conditionally expresses different elements of the engineered muscle-specific delivery system described herein or contains one or more cells that incorporates and / or expresses one or more elements of the engineered muscle-specific delivery system described herein.
[0272] In some embodiments, two or more of the elements expressed from the same or different regulatory element(s) can be combined in a single vector along with one or more additional vectors providing any components of the system not included in the first vector. Engineered muscle-specific delivery system polynucleotides (including but not limited to engineered muscle-specific targeting moiety polynucleotides) that are combined in a single vector may be arranged in any suitable orientation, such as one element located 5′ with respect to (“upstream” of) or 3′ with respect to (“downstream” of) a second element. The coding sequence of one element may be located on the same or opposite strand of the coding sequence of a second element, and oriented in the same or opposite direction. In some embodiments, a single promoter drives expression of a transcript encoding one or more engineered muscle-specific targeting moiety polynucleotides, embedded within one or more intron sequences (e.g., each in a different intron, two or more in at least one intron, or all in a single intron). In some embodiments, two or more engineered muscle-specific targeting moiety polynucleotides can be operably linked to and expressed from the same promoter.Vector Features
[0273] The vectors can include additional features that can confer one or more functionalities to the vector, the polynucleotide to be delivered, a virus particle produced there from, or polypeptide expressed thereof. Such features include, but are not limited to, regulatory elements, selectable markers, molecular identifiers (e.g. molecular barcodes), stabilizing elements, and the like. It will be appreciated by those skilled in the art that the design of the expression vector and additional features included can depend on such factors as the choice of the host cell to be transformed, the level of expression desired, etc.Regulatory Elements
[0274] In embodiments, the polynucleotides and / or vectors thereof described herein (such as the engineered muscle-specific targeting moiety polynucleotides of the present invention) can include one or more regulatory elements that can be operatively linked to the polynucleotide. The term “regulatory element” is intended to include promoters, enhancers, internal ribosomal entry sites (IRES), and other expression control elements (e.g., transcription termination signals, such as polyadenylation signals and poly-U sequences). Such regulatory elements are described, for example, in Goeddel, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990). Regulatory elements include those that direct constitutive expression of a nucleotide sequence in many types of host cell and those that direct expression of the nucleotide sequence only in certain host cells (e.g., tissue-specific regulatory sequences). A tissue-specific promoter can direct expression primarily in a desired tissue of interest, such as muscle, neuron, bone, skin, blood, specific organs (e.g., liver, pancreas), or particular cell types (e.g., lymphocytes). Regulatory elements may also direct expression in a temporal-dependent manner, such as in a cell-cycle dependent or developmental stage-dependent manner, which may or may not also be tissue or cell-type specific. In some embodiments, a vector comprises one or more pol III promoter (e.g., 1, 2, 3, 4, 5, or more pol III promoters), one or more pol II promoters (e.g., 1, 2, 3, 4, 5, or more pol II promoters), one or more pol I promoters (e.g., 1, 2, 3, 4, 5, or more pol I promoters), or combinations thereof. Examples of pol III promoters include, but are not limited to, U6 and H1 promoters. Examples of pol II promoters include, but are not limited to, the retroviral Rous sarcoma virus (RSV) LTR promoter (optionally with the RSV enhancer), the cytomegalovirus (CMV) promoter (optionally with the CMV enhancer) (see, e.g., Boshart et al, Cell, 41:521-530 (1985)), the SV40 promoter, the dihydrofolate reductase promoter, the 0-actin promoter, the phosphoglycerol kinase (PGK) promoter, and the EF1α promoter. Also encompassed by the term “regulatory element” are enhancer elements, such as WPRE; CMV enhancers; the R-U5′ segment in LTR of HTLV-I (Mol. Cell. Biol., Vol. 8(1), p. 466-472, 1988); SV40 enhancer; and the intron sequence between exons 2 and 3 of rabbit β-globin (Proc. Natl. Acad. Sci. USA., Vol. 78(3), p. 1527-31, 1981).
[0275] In some embodiments, the regulatory sequence can be a regulatory sequence described in U.S. Pat. No. 7,776,321, U.S. Pat. Pub. No. 2011 / 0027239, and PCT publication WO 2011 / 028929, the contents of which are incorporated by reference herein in their entirety. In some embodiments, the vector can contain a minimal promoter. In some embodiments, the minimal promoter is the Mecp2 promoter, tRNA promoter, or U6. In a further embodiment, the minimal promoter is tissue specific. In some embodiments, the length of the vector polynucleotide the minimal promoters and polynucleotide sequences is less than 4.4 Kb.
[0276] To express a polynucleotide, the vector can include one or more transcriptional and / or translational initiation regulatory sequences, e.g. promoters, that direct the transcription of the gene and / or translation of the encoded protein in a cell. In some embodiments a constitutive promoter may be employed. Suitable constitutive promoters for mammalian cells are generally known in the art and include, but are not limited to SV40, CAG, CMV, EF-1α, β-actin, RSV, and PGK. Suitable constitutive promoters for bacterial cells, yeast cells, and fungal cells are generally known in the art, such as a T-7 promoter for bacterial expression and an alcohol dehydrogenase promoter for expression in yeast.
[0277] In some embodiments, the regulatory element can be a regulated promoter. “Regulated promoter” refers to promoters that direct gene expression not constitutively, but in a temporally- and / or spatially-regulated manner, and includes tissue-specific, tissue-preferred and inducible promoters. In some embodiments, the regulated promoter is a tissue specific promoter as previously discussed elsewhere herein. Regulated promoters include conditional promoters and inducible promoters. In some embodiments, conditional promoters can be employed to direct expression of a polynucleotide in a specific cell type, under certain environmental conditions, and / or during a specific state of development. Suitable tissue specific promoters can include, but are not limited to, liver specific promoters (e.g. APOA2, SERPIN A1 (hAAT), CYP3A4, and MIR122), pancreatic cell promoters (e.g. INS, IRS2, Pdx1, Alx3, Ppy), cardiac specific promoters (e.g. Myh6 (alpha MHC), MYL2 (MLC-2v), TNI3 (cTnl), NPPA (ANF), Slc8a1 (Ncx1)), central nervous system cell promoters (SYN1, GFAP, INA, NES, MOBP, MBP, TH, FOXA2 (HNF3 beta)), skin cell specific promoters (e.g. FLG, K14, TGM3), immune cell specific promoters, (e.g. ITGAM, CD43 promoter, CD14 promoter, CD45 promoter, CD68 promoter), urogenital cell specific promoters (e.g. Pbsn, Upk2, Sbp, Fer1l4), endothelial cell specific promoters (e.g. ENG), pluripotent and embryonic germ layer cell specific promoters (e.g. Oct4, NANOG, Synthetic Oct4, T brachyury, NES, SOX17, FOXA2, MIR122), and muscle cell specific promoter (e.g. Desmin). Other tissue and / or cell specific promoters are discussed elsewhere herein and can be generally known in the art and are within the scope of this disclosure.
[0278] Inducible / conditional promoters can be positively inducible / conditional promoters (e.g. a promoter that activates transcription of the polynucleotide upon appropriate interaction with an activated activator, or an inducer (compound, environmental condition, or other stimulus) or a negative / conditional inducible promoter (e.g. a promoter that is repressed (e.g. bound by a repressor) until the repressor condition of the promotor is removed (e.g. inducer binds a repressor bound to the promoter stimulating release of the promoter by the repressor or removal of a chemical repressor from the promoter environment). The inducer can be a compound, environmental condition, or other stimulus. Thus, inducible / conditional promoters can be responsive to any suitable stimuli such as chemical, biological, or other molecular agents, temperature, light, and / or pH. Suitable inducible / conditional promoters include, but are not limited to, Tet-On, Tet-Off, Lac promoter, pBad, AlcA, LexA, Hsp70 promoter, Hsp90 promoter, pDawn, XVE / OlexA, GVG, and pOp / LhGR.
[0279] Where expression in a plant cell is desired, the components of the engineered AAV capsid system described herein are typically placed under control of a plant promoter, i.e. a promoter operable in plant cells. The use of different types of promoters is envisaged. In some embodiments, inclusion of a engineered AAV capsid system vector in a plant can be for AAV vector production purposes.
[0280] A constitutive plant promoter is a promoter that is able to express the open reading frame (ORF) that it controls in all or nearly all of the plant tissues during all or nearly all developmental stages of the plant (referred to as “constitutive expression”). One non-limiting example of a constitutive promoter is the cauliflower mosaic virus 35S promoter. Different promoters may direct the expression of a gene in different tissues or cell types, or at different stages of development, or in response to different environmental conditions. In particular embodiments, one or more of the engineered AAV capsid system components are expressed under the control of a constitutive promoter, such as the cauliflower mosaic virus 35S promoter issue-preferred promoters can be utilized to target enhanced expression in certain cell types within a particular plant tissue, for instance vascular cells in leaves or roots or in specific cells of the seed. Examples of particular promoters for use in the engineered AAV capsid system are found in Kawamata et al., (1997) Plant Cell Physiol 38:792-803; Yamamoto et al., (1997) Plant J 12:255-65; Hire et al, (1992) Plant Mol Biol 20:207-18, Kuster et al, (1995) Plant Mol Biol 29:759-72, and Capana et al., (1994) Plant Mol Biol 25:681-91.
[0281] Examples of promoters that are inducible and that can allow for spatiotemporal control of gene editing or gene expression may use a form of energy. The form of energy may include but is not limited to sound energy, electromagnetic radiation, chemical energy and / or thermal energy. Examples of inducible systems include tetracycline inducible promoters (Tet-On or Tet-Off), small molecule two-hybrid transcription activations systems (FKBP, ABA, etc.), or light inducible systems (Phytochrome, LOV domains, or cryptochrome)., such as a Light Inducible Transcriptional Effector (LITE) that direct changes in transcriptional activity in a sequence-specific manner. The components of a light inducible system may include one or more elements of the engineered muscle-specific delivery system described herein, a light-responsive cytochrome heterodimer (e.g. from Arabidopsis thaliana), and a transcriptional activation / repression domain. In some embodiments, the vector can include one or more of the inducible DNA binding proteins provided in PCT publication WO 2014 / 018423 and US Publications, 2015 / 0291966, 2017 / 0166903, 2019 / 0203212, which describe e.g. embodiments of inducible DNA binding proteins and methods of use and can be adapted for use with the present invention.
[0282] In some embodiments, transient or inducible expression can be achieved by including, for example, chemical-regulated promotors, i.e. whereby the application of an exogenous chemical induces gene expression. Modulation of gene expression can also be obtained by including a chemical-repressible promoter, where application of the chemical represses gene expression. Chemical-inducible promoters include, but are not limited to, the maize ln2-2 promoter, activated by benzene sulfonamide herbicide safeners (De Veylder et al., (1997) Plant Cell Physiol 38:568-77), the maize GST promoter (GST-ll-27, WO93 / 01294), activated by hydrophobic electrophilic compounds used as pre-emergent herbicides, and the tobacco PR-1 a promoter (Ono et al., (2004) Biosci Biotechnol Biochem 68:803-7) activated by salicylic acid. Promoters which are regulated by antibiotics, such as tetracycline-inducible and tetracycline-repressible promoters (Gatz et al., (1991) Mol Gen Genet 227:229-37; U.S. Pat. Nos. 5,814,618 and 5,789,156) can also be used herein.
[0283] In some embodiments, the vector or system thereof can include one or more elements capable of translocating and / or expressing an engineered muscle-specific targeting moiety polynucleotide to / in a specific cell component or organelle. Such organelles can include, but are not limited to, nucleus, ribosome, endoplasmic reticulum, golgi apparatus, chloroplast, mitochondria, vacuole, lysosome, cytoskeleton, plasma membrane, cell wall, peroxisome, centrioles, etc.Selectable Markers and Tags
[0284] One or more of the engineered muscle-specific targeting moiety polynucleotides can be operably linked, fused to, or otherwise modified to include a polynucleotide that encodes or is a selectable marker or tag, which can be a polynucleotide or polypeptide. In some embodiments, the polynucleotide encoding a polypeptide selectable marker is incorporated in the engineered muscle-specific delivery system polynucleotide such that the selectable marker polynucleotide, when translated, is inserted between two amino acids between the N- and C-terminus of the engineered muscle-specific targeting moiety polypeptide (including but not limited to an engineered AAV capsid polypeptide) or at the N- and / or C-terminus of the engineered muscle-specific targeting moiety polypeptide (including but not limited to an engineered AAV capsid polypeptide). In some embodiments, the selectable marker or tag is a polynucleotide barcode or unique molecular identifier (UMI).
[0285] The term “barcode” as used herein refers to a short sequence of nucleotides (for example, DNA or RNA) that is used as an identifier for an associated molecule, such as a target molecule and / or target nucleic acid, or as an identifier of the source of an associated molecule, such as a cell-of-origin. A barcode may also refer to any unique, non-naturally occurring, nucleic acid sequence that may be used to identify the originating source of a nucleic acid fragment. Although it is not necessary to understand the mechanism of an invention, it is believed that the barcode sequence provides a high-quality individual read of a barcode associated with a single cell, a viral vector, labeling ligand (e.g., an aptamer), protein, shRNA, sgRNA or cDNA such that multiple species can be sequenced together.
[0286] Barcoding may be performed based on any of the compositions or methods disclosed in patent publication WO 2014047561 A1, compositions and methods for labeling of agents, incorporated herein in its entirety. In certain embodiments barcoding uses an error correcting scheme (T. K. Moon, Error Correction Coding: Mathematical Methods and Algorithms (Wiley, New York, ed. 1, 2005)). Not being bound by a theory, amplified sequences from single cells can be sequenced together and resolved based on the barcode associated with each cell.
[0287] In preferred embodiments, sequencing is performed using unique molecular identifiers (UMI). The term “unique molecular identifiers” (UMI) as used herein refers to a sequencing linker or a subtype of nucleic acid barcode used in a method that uses molecular tags to detect and quantify unique amplified products. A UMI is used to distinguish effects through a single clone from multiple clones. The term “clone” as used herein may refer to a single mRNA or target nucleic acid to be sequenced. The UMI may also be used to determine the number of transcripts that gave rise to an amplified product, or in the case of target barcodes as described herein, the number of binding events. In preferred embodiments, the amplification is by PCR or multiple displacement amplification (MDA).
[0288] It will be appreciated that the polynucleotide encoding such selectable markers or tags can be incorporated into a polynucleotide encoding one or more components of the engineered muscle-specific delivery system described herein in an appropriate manner to allow expression of the selectable marker or tag. Such techniques and methods are described elsewhere herein and will be instantly appreciated by one of ordinary skill in the art in view of this disclosure. Many such selectable markers and tags are generally known in the art and are intended to be within the scope of this disclosure.
[0289] Suitable selectable markers and tags include, but are not limited to, affinity tags, such as chitin binding protein (CBP), maltose binding protein (MBP), glutathione-S-transferase (GST), poly(His) tag; solubilization tags such as thioredoxin (TRX) and poly(NANP), MBP, and GST; chromatography tags such as those consisting of polyanionic amino acids, such as FLAG-tag; epitope tags such as V5-tag, Myc-tag, HA-tag and NE-tag; protein tags that can allow specific enzymatic modification (such as biotinylation by biotin ligase) or chemical modification (such as reaction with FlAsH-EDT2 for fluorescence imaging), DNA and / or RNA segments that contain restriction enzyme or other enzyme cleavage sites; DNA segments that encode products that provide resistance against otherwise toxic compounds including antibiotics, such as, spectinomycin, ampicillin, kanamycin, tetracycline, Basta, neomycin phosphotransferase II (NEO), hygromycin phosphotransferase (HPT)) and the like; DNA and / or RNA segments that encode products that are otherwise lacking in the recipient cell (e.g., tRNA genes, auxotrophic markers); DNA and / or RNA segments that encode products which can be readily identified (e.g., phenotypic markers such as β-galactosidase, GUS; fluorescent proteins such as green fluorescent protein (GFP), cyan (CFP), yellow (YFP), red (RFP), luciferase, and cell surface proteins); polynucleotides that can generate one or more new primer sites for PCR (e.g., the juxtaposition of two DNA sequences not previously juxtaposed), DNA sequences not acted upon or acted upon by a restriction endonuclease or other DNA modifying enzyme, chemical, etc.; epitope tags (e.g. GFP, FLAG- and His-tags), and, DNA sequences that make a molecular barcode or unique molecular identifier (UMI), DNA sequences required for a specific modification (e.g., methylation) that allows its identification. Other suitable markers will be appreciated by those of skill in the art.
[0290] Selectable markers and tags can be operably linked to one or more components of the engineered AAV capsid system described herein via suitable linker, such as a glycine or glycine serine linkers as short as GS or GG up to (GGGGG)3 (SEQ ID NO: 51) or (GGGGS)3 (SEQ ID NO: 56). Other suitable linkers are described elsewhere herein.
[0291] The vector or vector system can include one or more polynucleotides encoding one or more engineered muscle-specific targeting moiety(ies) described elsewhere herein. In some embodiments, the targeting moiety encoding polynucleotides can be included in the vector or vector system, such as a viral vector system, such that they are expressed within and / or on the virus particle(s) produced such that the virus particles can be targeted to specific cells, tissues, organs, etc. In some embodiments, one or more engineered muscle-specific targeting moiety encoding polynucleotides are included in the vector or vector system such that the engineered muscle-specific targeting moiety polynucleotide(s) and / or products expressed therefrom include the targeting moiety and can be targeted to specific cells, tissues, organs, etc., such as muscle cells, muscle tissue, or muscle containing organs (e.g. heart). In some embodiments, such as non-viral carriers, the targeting moiety can be attached to the carrier (e.g. polymer, lipid, inorganic molecule etc.) and can be capable of targeting the carrier and any attached or associated engineered muscle-specific targeting moiety polynucleotide(s) to specific cells, tissues, organs, etc., such as such as muscle cells, muscle tissue, or muscle containing organs (e.g. heart).Cell-Free Vector and Polynucleotide Expression
[0292] In some embodiments, the polynucleotide encoding one or more features of the engineered muscle-specific delivery system containing one or more engineered muscle-specific targeting moieties described h...
Claims
1. A composition comprising an adeno-associated virus (AAV) which comprises a targeting moiety effective to target a muscle cell and a polynucleotide encoding a cargo polynucleotide wherein the targeting moiety comprises a viral capsid protein comprising an n-mer motif, which comprises XmRGDXn, wherein X is any amino acid, m is 3, and n is 4, and wherein the n-mer motif is (a) inserted between any two native amino acids of the viral capsid protein, (b) replaces one or more native viral capsid protein amino acids, or both (a) and (b).
2. The composition of claim 1, wherein the n-mer motif is located in variable region VIII (VR-VIII).
3. The composition of claim 1, wherein the n-mer motif is inserted in the N or C terminus of any amino acid in amino acids 581 to 593 corresponding to the wild type AAV9 capsid protein.
4. The composition of claim 1, wherein the n-mer motif is located in variable region IV (VR-IV).
5. The composition of claim 1, wherein the n-mer motif is located in the N or C terminus of any amino acid in amino acids 452 and 460 corresponding to the wild type AAV9 capsid protein.
6. The composition of claim 1, wherein the n-mer motif is 10 amino acids in length.
7. The composition of claim 6, wherein the viral capsid protein comprises an AAVRh74 capsid protein with one, two, or three additional amino acid substitution, insertion, or deletion.
8. The composition of claim 6, wherein the amino acid sequence of the viral capsid protein is different from the amino acid sequence of the wild type AAVRh74 capsid protein by 11 amino acids.
9. The composition of claim 6, wherein the amino acid sequence of the viral capsid protein is different from the amino acid sequence of the wild type AAVRh74 capsid protein by 12 amino acids.
10. The composition of claim 3, wherein the n-mer motif is 10 amino acids, and wherein the viral capsid protein comprises an AAVRh74 capsid protein with one, two, or three additional amino acid substitution, insertion, or deletion.
11. The composition of claim 6, wherein the viral capsid protein comprises an AAV9 capsid protein with one, two, or three additional amino acid substitution, insertion or deletion.
12. The composition of claim 11, wherein the amino acid sequence of the viral capsid protein is different from the amino acid sequence of the wild type AAV9 capsid protein by 11 amino acids.
13. The composition of claim 11, wherein the amino acid sequence of the viral capsid protein is different from the amino acid sequence of the wild type AAV9 capsid protein by 12 amino acids.
14. The composition of claim 5, wherein the n-mer motif is 10 amino acids in length, and wherein the viral capsid protein comprises an AAV9 capsid protein with one, two, or three additional amino acid substitution, insertion, or deletion.
15. The composition of claim 1, wherein the cargo comprises a micro-dystrophin protein.
16. The composition of claim 13, wherein the cargo polynucleotide is operably linked to a promoter.
17. The composition of claim 16, wherein the promoter comprises a muscle-specific promoter.
18. The composition of claim 17, wherein the muscle-specific promoter comprises a MHCK7 promoter.
19. A method of targeting a muscle cell in a subject in need thereof having a muscular dystrophy comprising administering the composition of claim 1 to the subject, wherein the cargo is expressed in the muscle cell.
20. A method of targeting a muscle cell in a subject in need thereof having a muscular dystrophy comprising administering the composition of claim 6 to the subject, wherein the cargo is expressed in the muscle cell.
21. A method of targeting a muscle cell in a subject in need thereof having a muscular dystrophy comprising administering the composition of claim 10 to the subject, wherein the cargo is expressed in the muscle cell.
22. A method of targeting a muscle cell in a subject in need thereof having a muscular dystrophy comprising administering the composition of claim 14 to the subject, wherein the cargo is expressed in the muscle cell.
23. The method of claim 19, wherein the composition is capable of transducing the muscle cell more effectively than a composition comprising an AAV without the n-mer motif.
24. The method of claim 23, wherein the composition is capable of transducing the muscle cell by at least 50 times more effectively than the composition comprising an AAV without the n-mer motif.
25. The method of claim 23, wherein the composition is capable of transducing the muscle cell by about 50 to about 100 times more effectively than the composition comprising an AAV without the n-mer motif.
26. The method of claim 19, wherein the composition is capable of inducing faster kinetics of in vivo gene expression in the muscle cell compared to a composition comprising an AAV without the n-mer motif.
27. The method of claim 19, wherein the composition is capable of expressing a micro-dystrophin protein in the muscle cell.